Abstract 3104: Stromal fibroblasts promote progression of esophageal squamous cell carcinoma cells both in vitro and in vivo

Abstract

Abstract Objectives: The purpose of the study was to clarify the role of fibroblasts in the proliferation and growth pattern of esophageal squamous cell carcinoma and to experimentally study interactions between cancer cells and fibroblasts. Methods: We used 22 esophageal squamous cell carcinoma cell lines (mainly, TE series and KYSE series obtained from the RIKEN Cell Bank and the Japanese Collection of Research Bioresources, respectively) and human esophageal fibroblasts that had been established in our laboratory from surgical specimens. Cancer cells were cultured on Matrigel in the presence or absence of fibroblasts in the Matrigels, and their growth patterns were examined. Cell count assays were performed to examine the effects of the fibroblast culture supernatant, growth factors, cytokines, and various inhibitors on cancer cell growth. We also examined the influence of co-injection of fibroblasts on tumor growth in immunodeficient mice. Results: When plated on Matrigel, nearly all cell lines spread and grew in an invasive manner in the presence of fibroblasts, while in the absence of fibroblasts, most cell lines formed round or spheroidal colonies. Cell-count assay showed that in most cancer cells, cell proliferation was stimulated by addition of fibroblast supernatant. In particular, cell proliferation increased by more than 50% in 11 cell lines. Addition of hepatocyte growth factor (HGF) or interleukin-6 elicited a definitive proliferative response in only 2 and 3 cell lines, respectively. Both KYSE-220 and KYSE-50 proliferated in the presence of HGF, but the addition of MET inhibitor (PHA665752) suppressed the proliferation of only the former. In vivo tumor growth was stimulated by co-injection of fibroblasts in 9 of 22 cancer cell lines. Conclusions: Fibroblast had a profound influence on cell growth pattern on Matrigel. In many esophageal cancer cell lines, cell proliferation was promoted by the presence of fibroblasts both in vivo and in vitro. The stimulatory effect of fibroblast could be accounted for by HGF and/or interleukin-6 in some, but not in all, esophageal cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3104. doi:10.1158/1538-7445.AM2011-3104