Isolation and characterization of squamous cell carcinoma-derived stem-like cells: role in tumor formation

鳞状细胞癌衍生干细胞的分离和表征:在肿瘤形成中的作用

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作者:Katiuscia Dallaglio, Tiziana Petrachi, Alessandra Marconi, Francesca Truzzi, Roberta Lotti, Annalisa Saltari, Paolo Morandi, Mario Puviani, Antonino Maiorana, Dennis R Roop, Carlo Pincelli

Abstract

In human epidermis, keratinocyte stem cells (KSC) are characterized by high levels of β1-integrin, resulting in the rapid adhesion to type IV collagen. Since epithelial tumors originate from KSC, we evaluated the features of rapidly adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker, as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells proliferated to a greater extent and were more efficient in forming colonies than NRAD cells. RAD cells also migrated significantly better than NRAD cells. When seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD cells formed tumors 2-4 fold bigger than those derived from NRAD cells. In tumors derived from RAD cells, the mitotic index was significantly higher than in those derived from NRAD cells, while Ki-67 and survivin expression were more pronounced in RAD tumors. This study suggests that SCC RAD stem cells play a critical role in the formation and development of epithelial tumors.

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