title: Skin squamous cell carcinoma propagating cells increase with tumour progression and invasiveness.
abstract: Cancer stem cells have been described in various cancers including squamous tumours of the skin by their ability to reform secondary tumours upon transplantation into immunodeficient mice. Here, we used transplantation of limiting dilution of different populations of FACS-isolated tumour cells from four distinct mouse models of squamous skin tumours to investigate the frequency of tumour propagating cells (TPCs) at different stages of tumour progression. We found that benign papillomas, despite growing rapidly in vivo and being clonogenic in vitro, reformed secondary tumours upon transplantation at very low frequency and only when tumour cells were co-transplanted together with tumour-associated fibroblasts or endothelial cells. In two models of skin squamous cell carcinoma (SCC), TPCs increased with tumour invasiveness. Interestingly, the frequency of TPCs increased in CD34(HI) but not in CD34(LO) SCC cells with serial transplantations, while the two populations initially gave rise to secondary tumours with the same frequency. Our results illustrate the progressive increase of squamous skin TPCs with tumour progression and invasiveness and reveal that serial transplantation may be required to define the long-term renewal potential of TPCs.
authors.affiliation: IRIBHM, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Lapouge
authors.forename: Benjamin
authors.initials: B
authors.lastname: Beck
authors.forename: Dany
authors.initials: D
authors.lastname: Nassar
authors.forename: Christine
authors.initials: C
authors.lastname: Dubois
authors.forename: Sophie
authors.initials: S
authors.lastname: Dekoninck
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology*; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D018450:Disease Progression; D005434:Flow Cytometry; D006652:Histological Techniques; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000502:physiology*; D010212:Papilloma / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000503:physiopathology*; D033581:Stem Cell Transplantation; D013629:Tamoxifen
chemical_list: D018952:Antigens, CD34; D017931:DNA Primers; D013629:Tamoxifen