28 Expression of integrin [formula omitted]-11 by carcinoma associated fibroblasts modulates oral squamous cell carcinoma behavior

Abstract

Background and Aim We have previously shown that integrin α -11 is up-regulated in cancer associated fibroblasts (CAF) in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate its role on behavior of OSCC cells. Materials and methods Primary fibroblasts from OSCC patients with different levels of integrin α -11 expression were isolated and propagated in culture after informed consent. Cultured CAFs were transfected with retroviral vector constructs for down regulation of integrin α -11 or with empty vectors (as control), and then co-injected (100,000 CAFs) with luciferase transfected dysplastic oral keratinocytes (DOK cell line, 10,000 DOKluc per injection) in NOD/SCID-IL γ 2 deficient mice (n = 7 for each type of CAFs). Results The vectors targeted towards ITGA11 efficiently (more than 50%) suppressed gene expression in CAFs (CAF α 11−) at both protein and mRNA levels, when compared with empty vector transfected CAFs (CAF α 11+). CAF α 11− had similar morphology and growth potential as CAF α 11+. No tumors were formed when either of CAFs were injected in NOD/SCID-IL γ 2 deficient mice. Bigger tumors were formed when DOKluc were co-injected with empty vector CAFs (CAF α 11+) than with CAF α 11− (28.46 ± 6.46 mm3 versus 9.56 ± 3.31 mm3). The manual measurements of tumor volume were confirmed by the bioluminescence readings that showed an average reduction of 26% in the bioluminescence of tumors formed by DOKluc when co-injected with CAF α 11−. Conclusions The results of this study suggest that the expression of integrin α -11 by CAFs is able to modulate the behavior of OSCC cells.