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

BACKGROUND: Cancer-associated fibroblasts (CAFs) were shown to be important for tumour progression in head and neck squamous cell carcinomas (HNSCCs). Their heterogeneity and lack of specific markers is increasingly recognized. Integrin alpha 11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker. AIM: To investigate integrin alpha 11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (alpha-SMA), in HNSCC. METHODS: Fresh frozen (FF) and formalin-fixed paraffin- embedded (FFPE) samples from healthy volunteers (n = 24), oral lichen planus (OLP) (n = 32) and HNSCC (n = 106) were collected together with clinical data after ethical approval. Immunohistochemistry to detect integrin alpha 11 and alpha-SMA was performed on FF and FFPE samples. qPCR for integrin alpha 11 (ITGA11) and alpha-SMA (ACTA2) was performed on FF samples. Data were analysed using chi-square test and Kaplan-Meier survival analysis. RESULTS: Significantly higher levels of integrin alpha 11 and alpha-SMA at both protein and mRNA levels were found in HNSCC vs. normal controls and OLP. A strong correlation was found between integrin alpha 11 and alpha-SMA expression, and double staining showed their colocalization. Both integrin alpha 11 and alpha-SMA were detected surrounding metastatic islands. Expression of alpha-SMA at tumour front but not tumour centre correlated with patient survival. CONCLUSION: Integrin alpha 11 was overexpressed in HNSCC stroma and colocalized with alpha-SMA. Expression of alpha-SMA at tumour front but not tumour centre had prognostic value for survival, pinpointing the importance of assessing tumour front when evaluating stromal molecules as prognostic biomarkers.