Podoplanin, a novel marker of tumor-initiating cells in human squamous cell carcinoma A431.
Squamous cell carcinoma (SCC) is a malignant tumor that shows morphologic and phenotypic similarities to normally differentiated squamous epithelium. Thus, it may be an ideal model for seeking a marker of tumor-initiating cells (TICs) based on their morphology. Using the human SCC cell line A431, we found that, as a paradigm of cancer stem cells: (1) podoplanin(+) cells generate both podoplanin(+) and podoplanin(-) cells; (2) podoplanin(-) cells rarely generate podoplanin(+) cells; (3) podoplanin(+) cells have higher colony formation efficiency and tumorigenicity than podoplanin(-) cells; (4) localization and morphology of podoplanin(+) cells in a xenografted tumor derived from podoplanin(+) cells are similar with those in human oral SCC tissue or normal epithelium. Furthermore, podoplanin(+) A431 cells share sonic hedgehog and CD44 expression with stem cells in normal squamous epithelium. Hence, we concluded that podoplanin is a novel marker to enrich TICs with stem-cell-like properties from SCC cell line A431.
Laboratory of Cancer Biology, Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
Naho
N
Atsumi
Genichiro
G
Ishii
Motohiro
M
Kojima
Masaru
M
Sanada
Satoshi
S
Fujii
Atsushi
A
Ochiai
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D045744:Cell Line, Tumor; D053823:Hedgehog Proteins / Q000032:analysis; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D016513:Mice, SCID; D009061:Mouth Mucosa / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000737:chemistry*; D014183:Transplantation, Heterologous; D000098853:Podoplanin
D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin; C509239:SHH protein, human