title: CD44(high)CD24(low) molecular signature determines the Cancer Stem Cell and EMT phenotype in Oral Squamous Cell Carcinoma.
abstract: Almost all epithelial tumours contain cancer stem-like cells, which possess a unique property of self-renewal and differentiation. In oral cancer, several biomarkers including cell surface molecules have been exploited for the identification of this highly tumorigenic population. Implicit is the role of CD44 in defining CSCs but CD24 is not well-explored. Here we show that CD44(high)CD24(low) cells isolated from the oral cancer cell lines, not only express stem cell related genes but also exhibit Epithelial-to-Mesenchymal transition (EMT) characteristics. This CD44(high)CD24(low) population gives rise to all other cell types upon differentiation. Typical Cancer Stem Cell (CSC) phenotypes like increased colony formation, sphere forming ability, migration and invasion were also confirmed in CD44(high)CD24(low) cells. Drug transporters were found to be over-expressed in CD44(high)CD24(low) sub-population thereby contributing to elevated chemo-resistance. To validate our findings in-vivo, we determined the relative expression of CD44 and CD24 in clinical samples of OSCC patients. CD44 expression was consistently high whereas CD24 showed significantly lower expression in tumour tissues. Further, the gene expression profile of the CSC and non-CSC population unravels the molecular pathways which may contribute to stemness. We conclude that CD44(high)CD24(low) represents cancer stem-like cells in Oral Squamous Cell Carcinoma.
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Ghuwalewala
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Dishari
authors.initials: D
authors.lastname: Ghatak
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Pijush
authors.initials: P
authors.lastname: Das
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Sanjib
authors.initials: S
authors.lastname: Dey
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Shreya
authors.initials: S
authors.lastname: Sarkar
authors.affiliation: Department of Surgical Oncology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Neyaz
authors.initials: N
authors.lastname: Alam
authors.affiliation: Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India.
authors.forename: Chinmay K
authors.initials: CK
authors.lastname: Panda
authors.affiliation: Cancer Biology and Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India. Electronic address: susantarc@gmail.com.
authors.forename: Susanta
authors.initials: S
authors.lastname: Roychoudhury
mesh_terms: D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D051927:CD24 Antigen; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D014157:Transcription Factors