FGFR2-positive fibroblasts provide a suitable microenvironment for tumor development and progression in esophageal carcinoma

Abstract

Background & Aims: Tumor fibroblasts (TFs) have been suggested to play an essential role in the complex process of tumor-stroma interactions and tumorigenesis. The aim of the present study was to investigate the specific role of TF in the esophageal cancer microenvironment. Methods: An Affymetrix expressionmicroarray was used to compare gene expression profiles between six pairs of TFs and normal fibroblasts (NFs) from esophageal squamous cell carcinoma (ESCC). Differentially expressed genes were identified and a subset was validated by semi-quantitative reverse transcription-PCR (RT-PCR). Results: About 43% (126/292) of known deregulated genes in TFs were associated with cell proliferation, extracellular matrix remodeling, and immune response. Up-regulation of FGFR2, which showed the most significant change, was detected in all six tested TFs as compared to their paired NFs. A further study found that FGFR2-positive fibroblasts were only observed in tumor tissues and not in tumor-surrounding stromal tissues, suggesting that FGFR2 could be used as a TF-specific marker in ESCC. Moreover, conditioned medium (CM) from TFs was found to be able to promote ESCC tumor cell growth, migration and invasion in vitro. Conclusions: Our study provides new candidate genes for the esophageal cancer microenvironment. Based on our results, we hypothesize thatFGFR2(+)-TFs might provide cancer cells with a suitable microenvironment via secretion of proteins that could promote cancer development and progression through stimulation of cancer cell proliferation, induction of angiogenesis, inhibition of cell adhesion, enhancement of cell mobility, and promotion of the epithelial-mesenchymal transition (EMT).