Combination Treatment with All-Trans Retinoic Acid Prevents Cisplatin-Induced Enrichment of CD133+ Tumor-Initiating Cells and Reveals Heterogeneity of Cancer Stem Cell Compartment in Lung Cancer

摘要: The existence of specific cellular subpopulations within primary tumors with increased tumorigenic potential and chemotherapy resistance (tumor-initiating cells, TICs) holds great therapeutic implications. Resistant cells can remain quiescent for long periods be responsible local relapses metastasis. We others have previously described in non–small-cell lung cancer the presence cisplatin-resistant CD133+ tumor-initiating co-expression CXCR4 as possible indicator TICs disseminating potential. In this study, we report, by vitro cell fate tracing systems, heterogeneity TIC compartment a highly pool slowly dividing subpopulation, both containing but respectively enriched CD133+/CXCR4− CD133+/CXCR4+ cells. Pretreatment differentiating agent all-trans retinoic acid counteracts cisplatin specifically indicating effect on same effects are appreciable also vivo patient-derived xenografts, where several cycles treatment able to stably reduce fraction tumor dissemination. Thus, partially affecting heterogeneous compartment, therapy has promising counteracting reducing growth addition, our approach discloses further level complexity chemotherapy-resistant TICs, revealing phenotypical functional stem cancer.