Oral cancer stem cells drive tumourigenesis through activation of stromal fibroblasts

Abstract

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.

SOX2 promotes a cancer stem cell-like phenotype and local spreading in oral squamous cell carcinoma

“…It is well known that the OSCC core is populated by a small fraction of CSCs, which may represent the culprits behind the anchorage-independent growth, migration, and spreading of tumor cells [ 33 ]. The presence within the OSCC margins of a subpopulation of CSCs that may function as cancer-initiating cells and, thus.…”

“…These results were supported by TCGA analysis showing that the identified CSCs gene signature significantly correlates with advanced tumor stage, but not with OS, also in patients with HNSCC. [ 24 , 27 , 28 , 33 – 41 ]. The only exception was for CXCR4 , whose high expression in HNSCC samples appears to correlate with a better OS.…”

Characterization of adhesion, anti-adhesion, co-aggregation, and hydrophobicity of Helicobacter pylori and probiotic strains

“…Human oral squamous cell carcinoma (H357 cells), human colorectal adenocarcinoma cells (Caco-2), and human normal intestinal epithelial cell line-6 cells (HIEC-6 cells) were used in this study. All cells were cultured in Dulbecco's modified Eagle's medium (DMEM) 21 , 22 at 37 °C in 5% CO 2 .…”

Utility of CD44/CD24 in the Outcome and Prognosis of Oral Squamous Cell Carcinoma: A Systematic Review

“…CSCs show a marked propensity for self-renewal and heterologous differentiation [ 4 ]. They play an important role in therapeutic resistance, metastasis, apoptotic resistance, and tumorigenesis [ 13 , 14 , 18 ]. CD44 and CD24 are engaged in different functions during cancer metastasis and progression.…”