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Oral cancer stem cells drive tumourigenesis through activation of stromal fibroblasts
Author(s) -
AlMagsoosi Mohanad J. N.,
Lambert Daniel W.,
Ali Khurram Syed,
Whawell Simon A.
Publication year - 2021
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.13513
Subject(s) - cancer stem cell , cd44 , stem cell , stem cell marker , stromal cell , cancer research , cancer cell , biology , cancer , fibronectin , cancer associated fibroblasts , pathology , cell , immunology , medicine , microbiology and biotechnology , extracellular matrix , genetics
Background Cancer stem cells are responsible for tumour progression and chemoresistance. Fibroblasts surrounding a tumour also promote progression and fibroblast “activation” is an independent prognostic marker in oral cancer. Cancer stem cells may therefore promote tumourigenesis through communication with stromal fibroblasts. Methods Cancer stem cells were isolated from oral cancer cell lines by adherence to fibronectin or cisplatin resistance. Fibroblasts were exposed to conditioned medium from these cells, and the activation markers, alpha smooth muscle actin and interleukin‐6, were assessed using qPCR and immunofluorescence. Stem cell markers and smooth muscle actin were examined in oral cancer tissue using immunohistochemistry. Results Adherent and chemoresistant cells expressed increased levels of stem cell markers CD24, CD44 and CD29 compared with unsorted cells. Adherent cells exhibited lower growth rate, higher colony forming efficiency and increased cisplatin resistance than unsorted cells. Smooth muscle actin and Interleukin‐6 expression were increased in fibroblasts exposed to conditioned medium. In oral cancer tissue, there was a positive correlation between expression of αSMA and stem cell markers. Conclusions Adherence to fibronectin and chemoresistance isolates stem‐like cells that can activate fibroblasts, which together with a correlation between markers of both in vivo, provides a mechanism by which such cells drive tumourigenesis.