Integrin α11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression

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The underlying connective tissue stroma is essential for the maintenance of epithelial tissues in normal conditions 1. As the epithelium changes, the stroma predictably changes. Fibroblasts are connective tissue cells that play a central role in pathological events such as fibrosis and carcinogenesis 2. Increasing evidence demonstrates that the progression of carcinoma is not solely due to genetically altered tumour cells, but also a result of the interactions between transformed tumour cells and surrounding non‐neoplastic cell compartment 2. One example is the invasiveness of transformed keratinocytes that can be triggered by pro‐invasive signals from the stromal fibroblasts, one of the major cell types found in the stroma of carcinomas 3. Another study that indicated a major role for fibroblasts in carcinoma cell invasion showed that carcinoma cells invaded the underlying matrix by moving within tracks already shaped by fibroblasts 4. Nevertheless, the somehow established concept that stroma has a crucial role for carcinoma progression is now being challenged by very recent studies on pancreas adenocarcinoma 5. Regardless of their role for carcinoma progression, fibroblasts in the tumour stroma are most often activated. Several studies have described the activation of carcinoma‐associated fibroblasts (CAFs) and their transdifferentiation towards a myofibroblastic phenotype (expressing α‐SMA) in carcinoma arising in different locations, including head and neck squamous cell carcinoma (HNSCC) 7.
The presence of myofibroblasts in the stroma of tongue and oral cancer has been associated with poor prognosis by several studies 8. Integrin‐mediated interactions between extracellular matrix and the cytoskeleton seem to promote myofibroblast differentiation 12. Collagen‐binding integrins α1β1 13 and α2β1 14 were the first shown to influence myofibroblast differentiation under some conditions in vitro. Another collagen receptor, α11β1, has been also shown to regulate myofibroblast differentiation 15. Integrin α11 is expressed in many tissues in the embryo but disappears with maturation in adult tissues 16. However, it has been proved that its expression is upregulated in malignant conditions such as non‐small‐cell lung carcinoma, where it has been suggested to be connected to cancer cell growth 17. We also showed previously overexpression of integrin α11 in CAFs isolated from oral squamous cell carcinomas, but its expression in patient samples with either oral or head and neck carcinomas was not investigated at that time 19.
The aim of this study was to investigate the expression pattern of integrin α11 in HNSCC and its correlation with the well‐known myofibroblast marker α‐SMA.
We provide here data showing that integrin α11 is overexpressed in stroma of primary HNSCC and that it colocalizes with α‐SMA. Expression of α‐SMA at tumour front but not tumour centre had prognostic value for patient survival, indicating that tumour front is essential for evaluating stromal molecules as prognostic biomarkers in HNSCC.
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