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

Himalaya Parajuli,Ingrid Christoffersen,Anne Chr Johannessen,Tarig Osman,Stein Lybak,Kathrine Skarstein,Siren Abrahamsen,Muy‐Teck Teh,Daniela Elena Costea,Evelyn Neppelberg,Donald Gullberg

doi:10.1111/jop.12493

Abstract

BackgroundCancer‐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 α11 was recently shown to be expressed by CAFs and might serve as a specific CAF marker.AimTo investigate integrin α11 expression and its correlation with the expression of a well‐known marker of CAF, alpha smooth muscle actin (α‐SMA), in HNSCC.MethodsFresh 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 α11 and α‐SMA was performed on FF and FFPE samples. qPCR for integrin α11 (ITGA11) and α‐SMA (ACTA2) was performed on FF samples. Data were analysed using chi‐square test and Kaplan–Meier survival analysis.ResultsSignificantly higher levels of integrin α11 and α‐SMA at both protein and mRNA levels were found in HNSCC vs. normal controls and OLP. A strong correlation was found between integrin α11 and α‐SMA expression, and double staining showed their colocalization. Both integrin α11 and α‐SMA were detected surrounding metastatic islands. Expression of α‐SMA at tumour front but not tumour centre correlated with patient survival.ConclusionIntegrin α11 was overexpressed in HNSCC stroma and colocalized with α‐SMA. Expression of α‐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.

Highlights

The underlying connective tissue stroma is essential for the maintenance of epithelial tissues in normal conditions [1]
We showed previously overexpression of integrin a11 in Cancer-associated fibroblasts (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]
We provide here data showing that integrin a11 is overexpressed in stroma of primary head and neck squamous cell carcinomas (HNSCCs) and that it colocalizes with alpha smooth muscle actin (a-SMA)

Summary

Introduction

The underlying connective tissue stroma is essential for the maintenance of epithelial tissues in normal conditions [1]. One example is the invasiveness of transformed keratinocytes that can be triggered by proinvasive signals from the stromal fibroblasts, one of the Integrin a11 in head and neck cancer Parajuli et al.268 major cell types found in the stroma of carcinomas [3]. 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. 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. Immunohistochemistry to detect integrin a11 and a-SMA was performed on FF and FFPE samples. A strong correlation was found between integrin a11 and a-SMA

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Results

Conclusion