Abstract
BackgroundOral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis. Cancer-associated fibroblasts (CAFs) play an important role in the complex processes of cancer stroma interaction and tumorigenesis. This study aims to determine the role of CAFs in the development and progression of OTSCC.MethodsImmunohistochemistry was performed to evaluate the frequency and distribution of CAFs in 178 paraffin specimens from patients with OTSCC. Immunofluorescence, a cell proliferation assay, flow cytometry, migration and invasion assays and western blot analysis were used to study the effects of CAFs and the corresponding conditioned medium (CM) on the proliferation and invasion of OTSCC cell lines.ResultsStatistical analysis showed a strong correlation between the frequency and distribution of CAFs and the clinicopathological characteristics of patients with cN0 OTSCC, including pathological stage (P = 0.001), T classification (P = 0.001), and N classification (P = 0.009). Survival analysis demonstrated a negative correlation of the frequency and distribution of CAFs with the overall survival and disease-free survival of patients with cN0 tongue squamous cell cancer (P = 0.009, 0.002, respectively); Cox regression analysis showed that the presence of CAFs (relative risk: 2.113, CI 1.461–3.015, P = 0.023) is an independent prognostic factor. A functional study demonstrated that CAFs and CM from CAFs could promote the growth, proliferation, mobility, invasion and even Epithelial Mesenchymal Transition (EMT) of OTSCC cells compared with NFs and CM from NFs.ConclusionsCAFs were an independent prognostic factor for patients with OTSCC. Compared with NFs, CAFs and their CM have the ability to promote the growth, proliferation, metastasis and even EMT of OTSCC cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0551-8) contains supplementary material, which is available to authorized users.
Highlights
Oral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis
Substantial evidence indicates that the interactions between tumor cells and their microenvironment are of great importance in the development and progression of cancer
The cancer stromal portion of a carcinoma is formed by the interaction of cancer stromal cells and cytokines in the extracellular matrix, which is produced by fibroblasts, macrophages and other inflammatory cells as well as blood/lymphatic capillaries [7]
Summary
Oral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis. Cancer-associated fibroblasts (CAFs) play an important role in the complex processes of cancer stroma interaction and tumorigenesis. Substantial evidence indicates that the interactions between tumor cells and their microenvironment are of great importance in the development and progression of cancer. A sub-population of cells in the cancer stroma, with a myofibroblast-like phenotype, has been termed cancer-associated fibroblasts (CAFs) [8, 9]. CAFs undergo changes in protein expression that represent an ‘activated’ myofibroblastic phenotype, which typically involves the up-regulation of markers such as α-smooth muscle actin (α-SMA) [10, 11]. By imitating activated ‘wound repair’ fibroblasts, CAFs are thought to promote the progression of carcinoma via the stimulation of epithelial cell growth, migration and invasion [5, 12, 13]
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