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Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation
Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy
Ospedale Civile di Sassuolo, Via Francesco Ruini, 2, 41049 Sassuolo (MO), Italy
Department of Laboratories and Pathologic Anatomy, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy
Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, Department of Dermatology, University of Colorado, Denver, CO 80045, USA
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 5 July 2013; in revised form: 3 September 2013 / Accepted: 10 September 2013 / Published: 26 September 2013
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.
Keywords: squamous cell carcinoma; stem cells; β1-integrin; tumor formation; survivin; rapidly adhering cells; skin; tumorigenesis; differentiation
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Dallaglio, K.; Petrachi, T.; Marconi, A.; Truzzi, F.; Lotti, R.; Saltari, A.; Morandi, P.; Puviani, M.; Maiorana, A.; Roop, D.R.; Pincelli, C. Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation. Int. J. Mol. Sci. 2013, 14, 19540-19555.
Dallaglio K, Petrachi T, Marconi A, Truzzi F, Lotti R, Saltari A, Morandi P, Puviani M, Maiorana A, Roop DR, Pincelli C. Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation. International Journal of Molecular Sciences. 2013; 14(10):19540-19555.
Dallaglio, Katiuscia; Petrachi, Tiziana; Marconi, Alessandra; Truzzi, Francesca; Lotti, Roberta; Saltari, Annalisa; Morandi, Paolo; Puviani, Mario; Maiorana, Antonino; Roop, Dennis R.; Pincelli, Carlo. 2013. "Isolation and Characterization of Squamous Cell Carcinoma-Derived Stem-like Cells: Role in Tumor Formation." Int. J. Mol. Sci. 14, no. 10: 19540-19555.