Wikipedia

Kwayoyin Ciwon Daji

Kwayoyin ciwon daji ( CSCs ), ya kasan ce kuma sune kwayoyin ciwon daji (wanda aka samo a cikin ciwace-ciwacen daji ko ciwon daji ) waɗanda ke da halaye masu alaƙa da kwayoyin halitta na al'ada, musamman ikon haifar da kuma duk nau'in tantanin halitta da kuma aka samu a cikin wani samfurin ciwon daji. Saboda haka CSCs suna da ƙari (tumor-forming), watakila ya bambanta da sauran kwayoyin cutar kansa marasa tumorigenic.[1] CSCs, na iya haifar da ciwace-ciwace ta hanyar tsarin ƙwayoyin cuta na sabuntawar kai da bambancewa cikin nau'ikan tantanin halitta da yawa. Irin waɗannan ƙwayoyin ana tsammanin zasu cigaba da kasancewa cikin ciwace-ciwacen ƙwayar cuta a matsayin jama'a daban-daban kuma suna haifar da koma baya da metastasis ta hanyar haifar da sabbin ciwace-ciwace. Sabili da haka, haɓaka takamaiman hanyoyin kwantar da hankali da aka yi niyya a CSCs, yana riƙe da bege don inganta rayuwa da ingancin rayuwar marasa lafiyar cutar kansa, musamman ga marasa lafiya da cututtukan metastatic .

Kwayoyin Ciwon Daji
cell type (en) Fassara da Wikimedia duplicated page (en) Fassara
Bayanai
Ƙaramin ɓangare na stem cell (en) Fassara da cancer cell (en) Fassara
Alamomin
Hoto na 1: Ƙayyadadden ƙwayar cuta
Bayanin alamomin

Maganin ciwon daji da ake da su galibi an haɓaka su ne bisa nau'ikan dabbobi, inda aka yi la'akarin hanyoyin kwantar da hankali don haɓaka haɓakar ƙwayar cuta. Duk da haka, dabbobi ba su samar da cikakken samfurin cutar ɗan adam ba. Musamman, a cikin berayen, waɗanda kuma tsawon rayuwarsu ba su wuce shekaru biyu ba, sake dawowar ƙari yana da wuyar yin karatu.

Ingancin jiyya na ciwon daji shine, a farkon matakan gwaji, sau da yawa ana auna su ta hanyar raguwar ɓarna na ƙwayar cuta ( kashe kashi ). Kamar yadda CSCs, ke samar da ƙaramin rabo na ƙari, wannan ƙila ba lallai ba ne zaɓin magungunan da ke aiki musamman akan sel mai tushe. Ka'idar ta nuna cewa chemotherapies na al'ada suna kashe nau'i daban-daban ko bambance-bambancen sel, waɗanda ke zama mafi yawan ƙwayar cuta amma ba sa haifar da sababbin kwayoyin halitta. Yawan jama'ar CSC, waɗanda kuma suka haifar da ita, na iya zama ba a taɓa su ba kuma suna haifar da koma baya.

John Dick ne ya fara gano ƙwayoyin cutar kansa a cikin m myeloid leukemia a ƙarshen 1990s. Tun daga farkon 2000s, sun kasance babban binciken bincike kan kansa. [2] An tsara kalmar da kanta a cikin takarda da aka ambata sosai a cikin 2001, ta masana ilimin halitta Tannishtha Reya, Sean J. Morrison, Michael F. Clarke da Irving Weissman . [3]

Samfurin yaɗuwar ƙwayar cuta.

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A cikin nau'ikan nau'ikan ƙari daban-daban, sel a cikin yawan ƙwayar ƙari suna nuna nau'ikan aiki iri -iri kuma ana samun ciwace-ciwace daga sel masu iya yaduwa iri-iri da bambanta . [4] Wannan nau'in nau'in nau'in nau'in nau'in ciwon daji ya haifar da ƙirƙirar nau'o'in yaduwa da yawa don yin lissafin nau'i-nau'i da bambance-bambance a cikin iyawar ƙwayar ƙwayar cuta: ƙwayar ciwon daji (CSC) da samfurin stochastic. Duk da haka, wasu ra'ayoyi sun tabbatar da cewa wannan ƙira ta wucin gadi ce, tun da dukkanin hanyoyin biyu suna aiki ne bisa ga madaidaicin halaye dangane da ainihin yawan ƙwayar cuta. Mahimmanci an lura cewa yayin da a cikin lafiyayyan ɗan adam epithelium na esophageal lafiyayyan nauyin yaduwa yana haɗuwa da stochastically rarraba basal epithelium. Bayan sauye-sauyensa zuwa epithelium na Barrett na farko, duk da haka, wani ƙaramin ɗaki mai ɗorewa yana bayyana wanda ke goyan bayan yaɗuwar epithelium yayin da shaidu guda ɗaya na sashin rarraba stochastically wanda ke ba da gudummawa ga kiyaye nama ya ɓace. Don haka, aƙalla don wasu kyallen jikin neoplastic, ɓangarorin ɓangarorin sel da aka keɓe suna kula da haɓaka girman sashin da aka canza [5]

 
Hoto 2: Matsayin salon salula na yau da kullun wanda ya ƙunshi sel mai tushe a koli, waɗanda ke haifar da gama-gari kuma mafi ƙuntataccen ƙwayoyin sel da kuma a ƙarshe nau'ikan tantanin halitta waɗanda suka ƙunshi nama na musamman.
 
Hoto na 3 . A cikin tsarin kwayar cutar kansa (CSC), CSCs kawai ke da ikon haifar da ƙari, dangane da abubuwan sabunta kansu da yuwuwar haɓakawa.

Samfurin kwayar cutar kansa.

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Samfurin kwayar cutar kansa, wanda kuma aka sani da Tsarin Hierarchical Model ya ba da shawarar cewa ciwace-ciwacen ciwace-ciwacen daji suna cikin tsari (CSCs suna kwance a koli [6] (Fig. 3). A cikin yawan ciwon daji na ciwace-ciwacen daji akwai ƙwayoyin cuta masu ciwon daji (CSC) waɗanda ke da ƙwayoyin tumorigenic kuma sun bambanta da ilimin halitta da sauran ƙananan jama'a [7] Suna da siffofi guda biyu: ikon su na dogon lokaci don sabunta kansu da kuma ikon su na bambanta. cikin zuriyar da ba su da ƙari amma har yanzu suna ba da gudummawa ga haɓakar ƙwayar cuta. Wannan samfurin yana ba da shawarar cewa kawai wasu ƙananan ƙwayoyin cuta na ciwon daji suna da ikon haifar da ci gaban ciwon daji, ma'ana cewa akwai takamaiman halaye (na zahiri) waɗanda za a iya gano su sannan kuma a yi niyya don lalata ƙwayar cuta na dogon lokaci ba tare da buƙatar yaƙi da cutar ba. duka ƙari. [8]

Stochastic model

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Domin tantanin halitta ya zama mai ciwon daji dole ne ya sami sauye-sauye masu yawa ga jerin DNA. Wannan samfurin tantanin halitta yana nuna waɗannan maye gurbi na iya faruwa ga kowane tantanin halitta a cikin jiki wanda ke haifar da ciwon daji. Ainihin wannan ka'idar tana ba da shawarar cewa duk ƙwayoyin cuta suna da ikon zama ƙari suna yin duk ƙwayoyin ƙari daidai da ikon sabunta kansu ko bambanta, wanda ke haifar da nau'in ƙari yayin da wasu na iya bambanta zuwa waɗanda ba CSCs [9] Ƙarfin tantanin halitta zai iya. Za a rinjayi abubuwan da ba a yi tsammani ba ko abubuwan epigenetic, wanda ke haifar da sel daban-daban a cikin duka ƙwayoyin tumorigenic da waɗanda ba na tumorigenic waɗanda ke haɗa ƙari. Dangane da "samfurin stochastic" (ko "samfurin juyin halitta na clonal") kowane kwayar cutar kansa a cikin ƙari zai iya samun ikon sabunta kansa da bambanta da yawa da nau'ikan zuriyar ƙwayoyin cutar kansa waɗanda ke lalata ƙari [10]

 
Hoto na 4: A cikin tsarin juyin halitta na clonal, duk ƙwayoyin da ba su da bambanci suna da irin wannan damar don canzawa zuwa kwayar cutar tumorigenic.

Waɗannan maye gurbi na iya ci gaba da tarawa da haɓaka juriya da dacewa da ƙwayoyin sel waɗanda ke ba su damar yin nasara ga sauran ƙwayoyin ƙari, waɗanda aka fi sani da ƙirar juyin halitta na somatic . Samfurin Juyin Halitta na clonal, wanda ke faruwa a cikin nau'in CSC duka da kuma samfurin stochastic, yana ƙaddamar da cewa ƙwayoyin ƙwayar cuta masu rikiɗawa tare da fa'idar girma sun fi sauran. Kwayoyin da ke cikin mafi yawan jama'a suna da irin wannan damar don fara haɓakar ƙari. [11] (Hoto 4).

[12] Waɗannan nau'ikan nau'ikan guda biyu ba su keɓanta juna ba, kamar yadda CSCs da kansu ke fuskantar juyin halitta na clonal. Don haka, na biyu mafi rinjaye na CSC na iya fitowa, idan maye gurbi yana ba da ƙarin kaddarorin mummuna[13] (Fig. 5).

 
Hoto na 5 : Duk nau'ikan ciwon daji na iya taka rawa wajen kula da ƙwayar cuta. Da farko, an tabbatar da ci gaban ƙari tare da takamaiman CSC (CSC1). Tare da ci gaban ƙari, wani CSC (CSC 2) na iya tasowa saboda zaɓin clonal . Haɓaka sabon ƙarin m CSC na iya haifar da samun ƙarin maye gurbi ko gyare-gyaren epigenetic .

Haɗa samfuran CSC da stochastic tare

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Wani bincike a cikin 2014 yana jayayya da rata tsakanin waɗannan nau'ikan rigima guda biyu za a iya daidaita su ta hanyar samar da wani bayani na daban-daban na ƙari. Suna nuna samfurin da ya haɗa da bangarorin biyu na Stochastic da CSC. Sun bincika filastik mai tushe na kansa wanda a cikinsa ƙwayoyin ƙwayoyin kansa za su iya canzawa tsakanin ƙwayoyin sel marasa ciwon daji (Non-CSC) da CSC ta wurin da ke tallafawa ƙarin ƙirar Stochastic.[14] Amma kasancewar duka nau'ikan halittu daban-daban waɗanda ba CSC ba da CSC suna goyan bayan ƙarin ƙirar CSC, suna ba da shawarar cewa duka samfuran biyu na iya taka muhimmiyar rawa a cikin nau'ikan ƙwayar cuta.

Samfurin rigakafin cutar kansa.

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Wannan samfurin yana nuna cewa kaddarorin rigakafi na iya zama mahimmanci don fahimtar tumorigenesis da iri-iri. Don haka, CSCs na iya zama da wuya a wasu ciwace-ciwacen daji,[15] amma wasu masu bincike sun gano cewa yawancin ƙwayoyin ƙwayar cuta na iya fara ciwace-ciwace idan an dasa su cikin ɓeraye marasa ƙarfi, [16] don haka suna tambayar dacewar CSCs da ba kasafai ba. Koyaya, duka sel masu tushe [17] da CSCs [18] suna da sifofin rigakafi na musamman waɗanda ke ba su juriya sosai ga rigakafin rigakafi. Don haka, CSCs kawai za su iya haifar da ciwace-ciwacen ƙwayar cuta a cikin marasa lafiya tare da aikin rigakafi na rigakafi, kuma gata na rigakafi na iya zama mahimmin ma'auni don gano CSCs. [19] Bugu da ƙari, samfurin yana nuna cewa CSCs, na iya kasancewa da farko sun dogara da ƙananan ƙwayoyin sel, kuma CSCs na iya aiki a can azaman tafki wanda maye gurbi zai iya tara shekaru da yawa ba tare da ƙuntatawa ta tsarin rigakafi ba. Ciwace-ciwacen ciwace-ciwace na iya girma idan: A) CSCs, sun rasa dogaro ga abubuwan alkuki (ƙananan ciwace-ciwacen ciwace-ciwacen daji), B) zuriyarsu masu yaɗuwa sosai, duk da haka da farko ƙwayoyin ƙwayar ƙwayar cuta ta al'ada ta haɓaka tana nufin tserewa rigakafi ko C) tsarin rigakafi na iya rasa ta. Ƙarfin ƙwayar cuta, misali saboda tsufa. [20]

Muhawara.

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Kasancewar CSCs yana ƙarƙashin muhawara, saboda yawancin binciken da aka samu babu sel tare da takamaiman halayen su. [21] Kwayoyin ciwon daji dole ne su kasance masu iya ci gaba da yaduwa da sabuntawar kansu don riƙe da yawancin maye gurbi da ake buƙata don carcinogenesis da kuma ci gaba da ci gaban ƙwayar cuta, tun da sel daban-daban (wanda aka ƙuntata ta Hayflick Limit [22] ) ba zai iya rarraba ba har abada. Don la'akarin warkewa, idan yawancin ƙwayoyin tumor suna da abubuwan da suka dace, niyya girman ƙari kai tsaye dabara ce mai inganci. Idan CSC ƴan tsiraru ne, niyya su na iya zama mafi inganci. Wani muhawara game da asalin CSCs - ko daga dysregulation na kwayoyin halitta na al'ada ko kuma daga ƙwararrun ƙwararrun jama'a waɗanda suka sami ikon sabunta kansu (wanda ke da alaƙa da batun ƙwayar ƙwayar ƙwayar cuta). Rikita wannan muhawara shine gano cewa yawancin ƙwayoyin cutar kansa suna nuna nau'in filastik a ƙarƙashin ƙalubale na warkewa, suna canza rubutun su zuwa yanayi mai kama da kara don guje wa halaka.[ana buƙatar hujja]

Shaida.

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Tabbatacciyar shaida ta farko don CSCs ta zo a cikin 1997. Bonnet da Dick sun keɓe ƙananan ƙwayoyin cutar sankarar bargo waɗanda suka bayyana alamar CD34, amma ba CD38 ba. [23] Mawallafa sun tabbatar da cewa CD34 + / CD38 - yawan yawan jama'a yana da ikon fara ciwace-ciwace a cikin berayen NOD/ SCID waɗanda suka yi kama da mai bayarwa. Shaida ta farko na ƙaƙƙarfan ƙwayar cutar kansar ƙwayar cuta mai kama da tantanin halitta ta biyo baya a cikin 2002, tare da gano ƙwayar cuta ta clonogenic, tantanin halitta wanda ke ware kuma yana da alaƙa daga gliomas na kwakwalwar ɗan adam balagagge. Ciwon daji na cortical glial na ɗan adam sun ƙunshi sel masu kama da jijiya waɗanda ke bayyana alamun astroglial da alamun neuronal a cikin vitro . [24] Kwayoyin ciwon daji da aka ware daga manyan gliomas na ɗan adam an nuna su haifar da ciwace-ciwacen ciwace-ciwacen daji waɗanda suka yi kama da ƙwayar mahaifa lokacin da aka cusa su cikin ƙirar linzamin kwamfuta tsirara. [25]

A cikin gwaje-gwajen bincike na ciwon daji, wasu lokuta ana allurar ƙwayoyin ƙari a cikin dabbar gwaji don kafa ƙari. Ana ci gaba da ci gaban cuta a cikin lokaci kuma ana iya gwada magungunan novel don ingancin su. Samuwar Tumor yana buƙatar dubunnan ko dubun duban sel don gabatar da su. A al'ada, an bayyana wannan ta hanyar rashin kyaun tsari (watau ƙwayoyin tumor sun rasa ƙarfinsu yayin canja wuri) ko mahimmancin mahimmancin ƙananan ƙwayoyin cuta, musamman mahallin sinadarai na ƙwayoyin allurar. Magoya bayan tsarin CSC suna jayayya cewa kaɗan ne kawai na ƙwayoyin allurar, CSCs, ke da yuwuwar haifar da ƙari. A cikin ɗan adam m myeloid cutar sankarar bargo, mitar wadannan kwayoyin bai wuce 1 cikin 10,000, ba. [26]

Ƙarin shaida ya zo daga histology . Yawancin ciwace-ciwacen ciwace-ciwace iri- iri ne kuma suna ƙunshe da nau'ikan tantanin halitta da yawa waɗanda suka fito daga sashin mai masaukin baki. Ciwon ƙwayar cuta yawanci ana riƙe shi ta hanyar metastases na ƙari. Wannan yana nuna cewa tantanin halitta da ya samar da su yana da ikon samar da nau'ikan tantanin halitta da yawa, alama ce ta al'ada ta kwayoyin halitta . [27]

Kasancewar ƙwayoyin cutar sankarar bargo ya haifar da bincike kan wasu cututtukan daji. Kwanan nan an gano CSCs a cikin ciwace-ciwace da yawa, gami da:

Samfuran injina da na lissafi.

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Da zarar an yi hasashe hanyoyin zuwa ciwon daji, yana yiwuwa a ƙirƙira ƙirar lissafi na tsinkaya, misali, bisa hanyar sashin sel . Misali, ana iya bayyana ci gaban sel marasa al'ada tare da takamaiman yuwuwar maye gurbi. Irin wannan samfurin ya annabta cewa maimaita cin mutunci ga sel balagagge yana ƙaruwa da samuwar zuriyar da ba ta dace ba da haɗarin ciwon daji. Tasirin asibiti na irin waɗannan samfuran ya kasance mara tushe.

Asalin.

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Hoto 6: Ƙungiya mai matsayi na ƙari bisa ga tsarin CSC

Asalin CSCs yanki ne mai aiki da bincike. Amsar na iya dogara da nau'in ƙari da nau'in phenotype . Ya zuwa yanzu dai hasashen cewa ciwace-ciwacen ciwace-ciwacen ciwace-ciwacen ciwace-ciwacen ciwace-ciwace sun samo asali ne daga “kwayoyin asali” guda daya ba a nuna su ta amfani da tsarin kwayar cutar kansar ba. Wannan shi ne saboda ƙwayoyin da ke haifar da ciwon daji ba su cikin ciwace-ciwacen mataki na ƙarshe.

Asalin hasashe sun haɗa da maye gurbi a cikin masu tasowa mai tushe ko sel masu tasowa, mutants a cikin sel mai tushe na manya ko manyan ƙwayoyin ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwararrun ƙwayoyin cuta waɗanda ke samun sifofi kamar kara. Waɗannan ka'idodin galibi suna mayar da hankali ne kan “kwayoyin asali” ƙari.

Hasashe.

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Maye gurbin kwayar halitta

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Hasashen "maye gurbi a cikin al'ummomin kwayoyin halitta yayin haɓakawa" hasashe yana iƙirarin cewa waɗannan al'ummomi masu tasowa suna canzawa sannan kuma su haifuwa ta yadda yawancin zuri'a ke raba maye gurbin. Wadannan sel 'ya'ya sun fi kusa da zama ciwace-ciwacen daji kuma adadin su yana kara yiwuwar maye gurbi mai cutar kansa. [44]

Manyan kwayoyin kara.

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Wata ka’idar tana danganta ƙwan ƙwan ƙwayoyin manya (ASC) tare da samuwar ƙari. Yawancin lokaci ana danganta wannan tare da kyallen takarda tare da yawan juzu'in tantanin halitta (kamar fata ko hanji ). A cikin waɗannan kyallen takarda, ASCs 'yan takara ne saboda yawan rarrabuwar tantanin halitta (idan aka kwatanta da yawancin ASCs) tare da tsawon rayuwar ASCs. Wannan haɗin yana haifar da ingantacciyar yanayin yanayi don maye gurbi don tarawa: tarin maye gurbi shine babban abin da ke haifar da farawar cutar kansa . Shaidu sun nuna cewa ƙungiyar tana wakiltar wani abu na gaske, kodayake an danganta takamaiman cutar kansa da wani takamaiman dalili.

De-banbantawa

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Bambance-bambancen sel da aka canza na iya haifar da halaye masu kama da kwayar halitta, suna nuna cewa kowane tantanin halitta zai iya zama kwayar cutar kansa. A wasu kalmomi, cikakkiyar bambance-bambancen tantanin halitta yana fuskantar maye gurbi ko siginar siginar salula waɗanda ke mayar da shi zuwa yanayi mai kama da tushe. An nuna wannan ra'ayi kwanan nan a cikin nau'ikan ciwon daji na prostate, inda sel waɗanda ke fuskantar jiyya na rashin ƙarfi na androgen ke bayyana suna canza rubutun su na ɗan lokaci zuwa na tantanin halitta mai kama da jijiyoyi, tare da ɓarna da kaddarorin masu yawa na wannan nau'in sel masu kama da kara.[ana buƙatar hujja]

Matsayi

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Ma'anar matsayi na ƙari yana iƙirarin cewa ƙari shine nau'in nau'in kwayoyin halitta masu kama da juna, dukansu suna raba wasu maye gurbi, amma sun bambanta a takamaiman nau'in phenotype . Ciwon daji yana ɗaukar nau'ikan sel masu tushe da yawa, ɗaya mafi kyau ga takamaiman mahalli da sauran layukan marasa nasara. Waɗannan layukan na biyu na iya zama mafi nasara a wasu wurare, ƙyale ƙwayar ƙwayar cuta ta daidaita, gami da daidaitawa ga saƙon warkewa. Idan daidai ne, wannan ra'ayi yana tasiri akan tsarin tsarin jiyya na musamman na ƙwayoyin cuta. [45] Irin wannan matsayi zai dagula yunƙurin nuna asalin.

Ganewa

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CSCs, wanda yanzu aka ruwaito a cikin mafi yawan ciwace-ciwacen mutum, ana gano su da kuma wadatar da su ta amfani da dabarun gano ƙwayoyin sel na yau da kullun waɗanda suke kama da juna a cikin karatu. [46] Waɗannan hanyoyin sun haɗa da rarrabuwar tantanin halitta mai kunna haske (FACS), tare da ƙwayoyin rigakafi da aka ba da umarni a alamomin saman tantanin halitta da hanyoyin aiki gami da ƙididdigar yawan jama'a ko gwajin Aldefluor. [47] Sakamakon wadatar CSC sannan ana shuka shi, a nau'ikan allurai daban-daban, a cikin ɓeraye masu ƙarancin rigakafi don tantance ƙarfin haɓakar ƙwayar cuta. Wannan in vivo assay ana kiransa ƙayyadaddun tantancewar dilution. Rukunin ƙwayar ƙwayar cuta wanda zai iya fara haɓaka ciwace-ciwacen ƙwayar cuta a ƙananan lambobi ana ƙara gwada ƙarfin sabuntawar kai a cikin binciken ƙwayar cuta.[48]

Hakanan za'a iya gano CSCs ta hanyar fitar da riniyoyin Hoechst da aka haɗa ta hanyar juriya da yawa (MDR) da kaset ɗin ATP-binding (ABC) Masu jigilar kaya.

Wata hanya kuma ita ce kima-samfurin kima. Yawancin sel masu tushe na al'ada irin su hematopoietic ko sel mai tushe daga kyallen takarda, a ƙarƙashin yanayin al'ada na musamman, suna samar da nau'i mai nau'i uku waɗanda zasu iya bambanta. Kamar yadda yake da sel mai tushe na al'ada, CSCs da ke ware daga kwakwalwa ko ciwace-ciwacen prostate suma suna da ikon samar da sassa masu zaman kansu. [49]

’Yan shekarun nan an ga bullowar hanyoyin da za a bi don gano kwayar cutar daji a cikin rodents na gwaji. A cikin irin wannan binciken, biyo bayan shigar da ciwon daji (yawanci ta hanyar aikace-aikacen mutagens), ana kunna kaset na kwayoyin halitta wanda ke haifar da bayyanar da alama mai sauƙin ganewa, misali koren furotin (GFP). Wannan ya shawo kan iyakokin hanyoyin al'ada (misali fasahar lakabin Bromodeoxyuridine (BrdU) na gargajiya da aka yi amfani da ita don gano ƙwayoyin jinkirin hawan keke a cikin dabbobi) kamar yadda hanyoyin ƙwayoyin cuta ke zama masu zaman kansu na sake zagayowar tantanin halitta kuma ana iya amfani da su a cikin vivo pulse-chase labeling don gano quiescent. /Slow-cycling Kwayoyin. [50] Wannan dabarar, alal misali, ta kasance kayan aiki don gano abin da ake kira rukunin Lgr5+ azaman sashin kwayar cutar kansa a cikin ciwon hanta da kuma nuna yuwuwar sa a matsayin maƙasudin warkewa. [51]

Bambance-bambance (alamomi)

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CSCs heterogeneity wani tafki ne na bambance-bambancen ƙwayoyin ƙari waɗanda ba su da bambanci waɗanda aka cika su ta sel waɗanda ke da duka ƙari da ƙwayar ƙwayar cuta kamar kaddarorin kuma suna da nau'ikan halitta da na rayuwa a cikin ƙwayar ƙwayar cuta guda ɗaya. Akwai ra'ayoyi guda biyu don bayyana yanayin phenotypic da na rayuwa na CSCs; bambancin clonal da ka'idar kwayar cutar kansa. Yayin da tsohuwar ka'idar ta nuna rawar da ke tattare da kwayoyin halitta, epigenetic da micro muhalli inda kwayar cutar ciwon daji ke zaune don samun halayen tumorigenic marasa bambanci. Ka'idar ta ƙarshe ta fi mayar da hankali kan halaye marasa kyau da aka samu ta hanyar sel masu tushe inda waɗannan ƙwayoyin da ba su da bambanci kuma suna da yawa sosai suna sake cika yawan ƙwayar ƙari.[52]

An gano CSCs a cikin nau'ikan ciwace-ciwace iri-iri. Yawanci, ana amfani da alamomi na musamman don sel mai tushe na yau da kullun don ware CSCs daga ciwace-ciwace da ciwace-ciwacen jini. Alamomi mafi akai-akai da ake amfani da su don warewar CSC sun haɗa da: CD133 (wanda kuma aka sani da PROM1 ), CD44, ALDH1A1, CD34, CD24 da EpCAM ( kwayoyin halitta adhesion cell epithelial, wanda kuma aka sani da antigen na musamman na epithelial, ESA ). [53]

CD133 (prominin 1) yanki ne na glycoprotein mai transmembrane guda biyar wanda aka bayyana akan CD34 + kara da sel masu zuwa, a cikin precursors na endothelial da sel kara na tayi . An gano shi ta amfani da epitope na glycosylated wanda aka sani da AC133.

EpCAM (Epithelial cell adhesion molecule, ESA, TROP1) shine hemophilic Ca 2+ - kwayoyin adhesion cell mai zaman kanta wanda aka bayyana akan basolateral surface na yawancin kwayoyin epithelial .

CD90 (THY1) shine glycosylphosylphosphatidylinositol glycoprotein wanda aka kafa a cikin membrane na plasma kuma yana shiga cikin jigilar sigina . Hakanan yana iya daidaita mannewa tsakanin thymocytes da thymic stroma.

CD44 (PGP1) kwayar halitta ce ta mannewa wacce ke da rawar gani a cikin siginar tantanin halitta, ƙaura da homing. Yana da isoforms da yawa, ciki har da CD44H, wanda ke nuna babban kusanci ga hyaluronate da CD44V wanda ke da kaddarorin metastatic.

CD24 (HSA) wani glycosylated glycosylphosphatidylinositol-anchored adhesion molecule, wanda ke da rawar haɗin gwiwa a cikin ƙwayoyin B da T.

CD200 (OX-2) wani nau'i ne na 1 membrane glycoprotein, wanda ke ba da siginar hanawa zuwa ƙwayoyin rigakafi ciki har da ƙwayoyin T, ƙwayoyin kisa na halitta da macrophages .

ALDH wani yanki ne na aldehyde dehydrogenase iyali na enzymes, wanda ke haifar da iskar shaka na aldehydes na aromatic zuwa carboxyl acid . Alal misali, yana da tasiri wajen canza retinol zuwa retinoic acid, wanda yake da mahimmanci don rayuwa.[54][55]

Na farko m malignancy daga wanda CSCs aka ware da kuma gano shi ne nono cancer kuma su ne mafi tsanani nazari. An wadatar da CSCs na nono a cikin CD44 + CD24 -/low, [56] SP [57] da ALDH + .[58][59] CSCs na nono a fili suna da bambanci . Maganar alamar CSC a cikin ƙwayoyin kansar nono a bayyane yake iri-iri ne kuma yawan CSC nono ya bambanta a cikin ciwace-ciwacen daji. [60] Dukansu CD44 + CD24 - da CD44 + CD24 + yawan yawan tantanin halitta sune ƙwayoyin farawar ƙari; duk da haka, CSC sun fi wadatuwa sosai ta amfani da bayanin martaba CD44 + CD49f hi CD133/2 hi .[61]

An ba da rahoton CSCs a yawancin ciwan kwakwalwa. An gano ƙwayoyin cuta ciki har da CD133, [62] SSEA-1 (antigen-takamaiman amfrayo-1), [63] EGFR [64] da CD44.[65] Amfani da CD133 don tantance ƙwayoyin ƙwaƙwalwar ƙwaƙwalwa na iya zama matsala saboda ƙwayoyin cuta na ƙwayar cuta a cikin wasu CD133 + Kwayoyin kwakwalwar CD133 na CD133 na CD13 na CD13 - Kwayoyin kwakwalwa .

An ba da rahoton CSC a cikin ciwon daji na hanji. Don gano su, an yi amfani da alamomin sararin samaniya irin su CD133, CD44 [66] da ABCB5, [67] nazarin aikin ciki har da nazarin clonal [68] da kuma Aldefluor assay. [69] Yin amfani da CD133 azaman tabbataccen alama don CSCs na hanji ya haifar da saɓani. Epitope na AC133, amma ba sunadaran CD133 ba, an bayyana shi musamman a cikin CSCs na hanji kuma an rasa bayanin sa akan bambancewa. [70] Bugu da ƙari, CD44 + ƙwayoyin ciwon daji na hanji da ƙarin ƙananan juzu'i na CD44 + EpCAM + yawan tantanin halitta tare da CD166 suna haɓaka nasarar haɓakar ƙwayar cuta.

An ba da rahoton CSC da yawa a cikin prostate,[71] huhu da sauran gabobin da yawa, gami da hanta, pancreas, koda ko ovary . A cikin ciwon daji na prostate, an gano ƙwayoyin farawar tumor a cikin CD44 +[72] tantanin halitta kamar CD44 + α2β1 +,[73] TRA-1-60 + CD151 + CD166 + [74] ko ALDH + [75] yawan adadin sel. . An ba da rahoton alamomin sakawa na huhu na CSC, ciki har da CD133 +, [76] ALDH +, [77] CD44 + [78] da furotin oncofetal 5T4 + . [79]

Metastasis

gyara sashe

Metastasis shine babban dalilin mutuwar ƙari. Duk da haka, ba kowane ƙwayar ƙwayar cuta ba zai iya yin metastasize. [80] Wannan yuwuwar ya dogara da abubuwan da ke ƙayyade girma, angiogenesis, mamayewa da sauran matakai na asali.

Epithelial-mesenchymal canji

gyara sashe

A cikin ciwace-ciwacen ciwace-ciwace, ana ɗaukar canjin epithelial-mesenchymal (EMT) a matsayin lamari mai mahimmanci.[81] EMT da jujjuya juyi daga mesenchymal zuwa nau'in nau'in nau'in nau'in nau'in halitta ( MET ) suna shiga cikin haɓakar amfrayo, wanda ya haɗa da rushewar homeostasis na sel na epithelial da kuma samun nau'in yanayin ƙaura na mesenchymal. [82] EMT ya bayyana ana sarrafa shi ta hanyoyin canonical kamar WNT da canza yanayin girma β . [83]

Muhimmin fasalin EMT shine asarar membrane E-cadherin a cikin haɗin gwiwar adherens, inda β-catenin na iya taka muhimmiyar rawa. Canja wurin β-catenin daga haɗin gwiwar adherens zuwa tsakiya na iya haifar da asarar E-cadherin kuma daga baya zuwa EMT. Nuclear β-catenin a fili zai iya kai tsaye, ta hanyar rubutawa ta kunna abubuwan da ke da alaƙa da EMT, irin su E-cadherin gene repressor SLUG (wanda aka fi sani da SNAI2 ). [84] Kayan aikin injiniya na ƙwayar cuta, irin su hypoxia, na iya ba da gudummawa ga rayuwa ta CSC da kuma m metastatic ta hanyar daidaitawa na hypoxia inducible dalilai ta hanyar hulɗa tare da ROS ( jinsunan oxygen mai amsawa ).[85][86]

Kwayoyin Tumor da ke jurewa EMT na iya zama madogara ga ƙwayoyin cutar kansa na metastatic, ko ma CSCs na metastatic. [87] [88] A cikin gefen ɓarna na ciwon daji na pancreatic, an bayyana sassan CD133 + CXCR4 + (mai karɓa don CXCL12 chemokine wanda aka fi sani da SDF1 ligand ). Waɗannan sel sun nuna ƙarfin ƙaura fiye da takwaransu CD133 + CXCR4 - sel, amma duka biyun sun nuna irin ƙarfin haɓakar ƙari.[89] Haka kuma, hana mai karɓar CXCR4 ya rage yuwuwar metastatic ba tare da canza ƙarfin tumorigenic ba.[90]

Tsarin magana mai mataki biyu

gyara sashe
 
Hoto na 7: Ma'anar ƙaura daga ƙwayoyin cutar kansa (MSC). Kwayoyin ciwon daji na tsaye suna kunshe a cikin carcinomas na farko kuma ana iya gano waɗannan sel a cikin bambancin tsakiyar yankin ƙari. Muhimmin mataki zuwa ga malignant shi ne shigar da epithelial mesenchymal miƙa mulki (EMT) a cikin tsaye ciwon daji stem cell (SCS), wanda ya zama mobile ko ƙaura kansa kara Kwayoyin. Kwayoyin karawa suna rarraba asymmetrically. Kwayoyin 'ya'ya daya za su fara yaduwa da bambanta. Ragowar MCS na yin ƙaura daga ɗan gajeren nesa kafin a sami sabon sashin asymmetric, ko kuma ya yadu ta hanyoyin jini ko tasoshin lymphatic kuma yana haifar da metastasis.

A cikin ciwon nono CD44 + CD24 -/ ƙananan sel ana iya gano su a cikin ɓarkewar ƙwayar cuta. [91] Sabanin haka, an gano ƙarin adadin ƙwayoyin CD24 + a cikin metastases mai nisa a cikin masu cutar kansar nono. [92] Yana yiwuwa CD44 + CD24 -/ ƙananan sel da farko su yi metastasize kuma a cikin sabon rukunin yanar gizon suna canza yanayin su kuma suna fuskantar iyakancewa. [93] Hasashen salon magana mai kashi biyu yana ba da shawarar nau'ikan ƙwayoyin cutar kansa guda biyu - tsaye (SCS) da wayar hannu (MCS). An saka SCS a cikin nama kuma suna dagewa a wurare daban-daban a duk tsawon ci gaban ƙari. Ana samun MCS a wurin mahaɗar ƙwayar cuta. Waɗannan sel da alama an samo su daga SCS ta hanyar siyan EMT na wucin gadi (Hoto 7). [94]

Tasiri

gyara sashe

CSCs suna da tasiri don maganin ciwon daji, ciki har da don gano cututtuka, zaɓin magungunan ƙwayoyi, rigakafin metastasis da dabarun sa baki.

Magani

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CSCs a zahiri sun fi juriya ga magungunan chemotherapeutic . Akwai manyan abubuwa guda 5 da suke haifar da hakan: [95]

1. Abubuwan da suke da shi na kare su daga haɗuwa da babban adadin magungunan cutar kansa.
2. Suna bayyana nau'ikan sunadaran transmembrane, irin su MDR1 da BCRP, waɗanda ke fitar da kwayoyi daga cikin cytoplasm.
3. Suna rarraba sannu a hankali, kamar manyan ƙwayoyin ƙwayoyin cuta suna yin haka, don haka ba a kashe su ta hanyar chemotherapeutic jamiái waɗanda ke yin niyya da sauri kwafi ta hanyar lalata DNA ko hana mitosis.
4. Suna daidaita sunadaran gyaran lalacewar DNA.
5. Ana siffanta su da wuce gona da iri na hanyoyin siginar anti-apoptotic.
Bayan jiyya na chemotherapy, CSCs masu tsira suna iya sake cika ƙwayar cutar da haifar da koma baya. Ƙarin magani da aka yi niyya don cire CSCs ban da ƙwayoyin somatic masu cutar kansa dole ne a yi amfani da su don hana wannan.

Yin niyya

gyara sashe

Zaɓan CSCs mai niyya na iya ba da damar jiyya na ciwace-ciwacen da ba za a iya sake su ba, da kuma hana metastasis da sake dawowa. Hasashen yana nuna cewa akan kawar da CSC, ciwon daji na iya komawa baya saboda bambance-bambance da/ko mutuwar tantanin halitta.[ana buƙatar hujja] Ƙirar ƙwayoyin ƙwayar cuta waɗanda suke CSCs don haka suna buƙatar kawar da su ba a sani ba. [96]

Nazarin ya nemi takamaiman alamomi da kuma sa hannu na ƙwayar cuta da ƙwayoyin cuta waɗanda ke bambanta CSCs daga wasu. [97] A cikin 2009, masana kimiyya sun gano fili salinomycin, wanda zaɓaɓɓen ya rage yawan adadin nono CSCs a cikin mice fiye da 100-ninka dangane da Paclitaxel, wani wakili na chemotherapeutic da aka saba amfani dashi. [98] Wasu nau'ikan kwayoyin cutar kansa na iya tsira da magani tare da salinomycin ta hanyar autophagy, [99] ta yadda sel ke amfani da gabobin kwayoyin acidic kamar lysosomes don lalatawa da sake sarrafa wasu nau'ikan sunadaran. Yin amfani da masu hana autophagy na iya kashe kwayoyin cutar kansa da ke rayuwa ta hanyar autophagy.[100]

The cell surface receptor interleukin-3 receptor-alpha (CD123) an overexpressed a kan CD34+CD38-leukemic stem Kwayoyin (LSCs) a cikin m myelogenous cutar sankarar bargo (AML) amma ba a al'ada CD34 + CD38- kasusuwa marrow Kwayoyin. [101] Yin maganin berayen NOD/SCID da aka sawa AML tare da CD123-takamaiman antibody monoclonal mai lahani LSCs zuwa ga marrow na kasusuwa kuma ya rage yawan jama'ar AML gabaɗaya gami da adadin LSCs a cikin masu karɓar linzamin kwamfuta na biyu.[102]

Nazarin 2015 ya ƙunshi nanoparticles tare da miR-34a da ammonium bicarbonate kuma ya isar da su zuwa CSCs na prostate a cikin ƙirar linzamin kwamfuta. Sannan suka haska wurin da hasken Laser na kusa da infrared . Wannan ya sa nanoparticles su kumbura sau uku ko fiye da girman su suna fashe endosomes kuma suna tarwatsa RNA a cikin tantanin halitta. miR-34a na iya rage matakan CD44. [103][104]

Wani bincike na 2018 ya gano masu hana dangin ALDH1A na enzymes kuma ya nuna cewa za su iya zaɓin rage ƙwayar ƙwayar cutar kansa a cikin layukan ƙwayoyin cutar kansar ovarian da yawa.[105]

Hanyoyi

gyara sashe

Ƙirƙirar sababbin magunguna don ƙaddamar da CSCs yana buƙatar fahimtar hanyoyin salula waɗanda ke daidaita yaduwar kwayar halitta. Ci gaba na farko a wannan yanki an yi su ne tare da kwayoyin halitta na hematopoietic (HSCs) da kuma takwarorinsu da suka canza a cikin cutar sankarar bargo, cutar da aka fi fahimtar asalin CSCs. Kwayoyin sassa na gabobin da yawa suna raba hanyoyin salon salula iri ɗaya da cutar sankarar bargo ta HSCs.

Za a iya canza kwayar halitta ta al'ada zuwa CSC ta hanyar dysregulation na yaduwa da hanyoyin bambance-bambancen da ke sarrafa shi ko ta hanyar haifar da ayyukan oncoprotein .

BMI-1

gyara sashe

An gano ƙungiyar Polycomb mai jujjuya rubutun Bmi -1 azaman ƙwayar cuta ta gama gari wacce aka kunna a cikin lymphoma [106] kuma daga baya aka nuna don daidaita HSCs. [107] An kwatanta rawar Bmi-1 a cikin ƙwayoyin tushe na jijiyoyi. [108] Hanyar yana bayyana yana aiki a cikin CSCs na ciwan kwakwalwar yara . [109]

Daraja

gyara sashe

Hanyar Notch tana taka rawa wajen sarrafa yaduwar kwayar halitta don nau'ikan tantanin halitta da yawa ciki har da hematopoietic, jijiyoyi da mammary [110] SCs. An ba da shawarar sassan wannan hanyar don yin aiki azaman oncogenes a cikin mammary [111] da sauran ciwace-ciwacen daji.

Wani reshe na hanyar siginar Notch wanda ya haɗa da ma'anar rubutun Hes3 yana daidaita yawancin ƙwayoyin al'ada tare da halayen CSC da aka samu daga marasa lafiya na glioblastoma. [112]

Sonic hedgehog da Wnt

gyara sashe

Waɗannan hanyoyin haɓakawa sune masu kula da SC.[113][114] Dukansu Sonic hedgehog (SHH) da hanyoyin Wnt galibi ana yin su ne a cikin ciwace-ciwacen daji. Koyaya, abubuwan rubutun Gli waɗanda SHH ke tsara su sun ɗauki sunansu daga gliomas, inda aka bayyana su sosai. Matsayin giciye yana wanzu tsakanin hanyoyin biyu kuma galibi ana kunna su tare. [115] Sabanin haka, a cikin ciwon daji na hanji siginar bushiya yana nuna adawa da Wnt. [116]

Sonic hedgehog blockers suna samuwa, kamar cyclopamine . Cyclopamine mai narkewar ruwa na iya zama mafi tasiri a maganin ciwon daji. DMAPT, wani abu mai narkewa na ruwa na parthenolide, yana haifar da danniya na oxidative kuma ya hana NF-κB siginar [117] don AML (cututtukan sankarar bargo) da yiwuwar myeloma da ciwon daji na prostate. Telomerase batun nazari ne a cikin ilimin halittar jiki na CSC. [118] GRN163L ( Imetelstat ) kwanan nan an fara shi a cikin gwaji don ƙaddamar da ƙwayoyin ƙwayoyin myeloma.

Siginar Wnt na iya zama mai zaman kanta daga abubuwan motsa jiki na yau da kullun, ta hanyar maye gurbi a cikin ƙwayoyin cuta na oncogenes da ƙwayoyin cuta masu hana ƙari waɗanda ke kunna su dindindin duk da cewa mai karɓa na yau da kullun bai sami sigina ba. β-catenin yana ɗaure zuwa abubuwan rubutu kamar furotin TCF4 kuma a hade kwayoyin suna kunna kwayoyin da suka dace. LF3 da ƙarfi yana hana wannan ɗauri a cikin vitro, a cikin layin salula da rage haɓakar ƙari a cikin ƙirar linzamin kwamfuta. Ya hana kwafi kuma ya rage karfin su na yin ƙaura, duk ba tare da cutar da ƙwayoyin lafiya ba. Babu kwayar cutar kansa da ta rage bayan magani. Sakamakon binciken shine samfurin " ƙirar magunguna na hankali", wanda ya haɗa da AlphaScreens da fasahar ELISA . [119]

Ci gaba da karatu

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  • Rajasekhar VK, ed. (2014). Cancer Stem Cells. Hoboken, New Jersey: Wiley. ISBN 9781118356166.
  • Milosevic V, et al. (January 2020). "Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5". Int. J. Cancer. 146 (1): 192–207. doi:10.1002/ijc.32419. PMID 31107974. S2CID 160014053.

Manazarta

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  20. ↑ Empty citation (help)
  21. ↑ Empty citation (help) [dead link]>
  22. ↑ Empty citation (help)
  23. ↑ Bonnet D, Dick JE (July 1997). "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell". Nature Medicine. 3 (7): 730–7. doi:10.1038/nm0797-730. PMID 9212098. S2CID 205381050.
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  110. ↑ Empty citation (help)
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  113. ↑ Milosevic, V. et al. Wnt/IL-1β/IL-8 autocrine circuitries control chemoresistancein mesothelioma initiating cells by inducing ABCB5.Int. J. Cancer, https://doi.org/10.1002/ijc.32419
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  116. ↑ Akiyoshi T, Nakamura M, Koga K, Nakashima H, Yao T, Tsuneyoshi M, Tanaka M, Katano M (July 2006). "Gli1, downregulated in colorectal cancers, inhibits proliferation of colon cancer cells involving Wnt signalling activation". Gut. 55 (7): 991–9. doi:10.1136/gut.2005.080333. PMC 1856354. PMID 16299030.
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  119. ↑ Hodge R (2016-01-25). "Hacking the programs of cancer stem cells". medicalxpress.com. Medical Express. Retrieved 2016-02-12.
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