Integrin a11 is overexpressed by tumour stroma of head and neck squamous cell carcinoma and correlates positively with alpha smooth muscle actin expression

Abstract

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 a11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker. AIM: To investigate integrin a11 expression and its correlation with the expression of a well-known marker of CAF, alpha smooth muscle actin (a-SMA), in HNSCC. METHODS: Fresh frozen (FF) and formalin-fixed paraf- fin-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 a11 and a-SMA was performed on FF and FFPE samples. qPCR for integrin a11 (ITGA11) and a-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 a11 and a-SMA at both protein and mRNA levels were found in HNSCC vs. normal controls and OLP. A strong correlation was found between integrin a11 and a-SMA expression, and double staining showed their colocalization. Both integrin a11 and a-SMA were detected surrounding metastatic islands. Expression of a-SMA at tumour front but not tumour centre correlated with patient survival. CONCLUSION: Integrin a11 was overexpressed in HNSCC stroma and colocalized with a-SMA. Expression of a-SMA at tumour front but not tumour centre had prognostic value for survival, pinpointing the importance of assessing tumour front when eva