Isolation and characterization of squamous cell carcinoma-derived stem-like cells: role in tumor formation.
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.
Department of Dermatology, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy. carlo.pincelli@unimore.it.
Katiuscia
K
Dallaglio
Tiziana
T
Petrachi
Alessandra
A
Marconi
Francesca
F
Truzzi
Roberta
R
Lotti
Annalisa
A
Saltari
Paolo
P
Morandi
Mario
M
Puviani
Antonino
A
Maiorana
Dennis R
DR
Roop
Carlo
C
Pincelli
D016475:3T3 Cells; D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D012097:Repressor Proteins / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D000077022:Survivin
C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D019012:Integrin beta1; D012097:Repressor Proteins; D000077022:Survivin