Abstract 1194: Fibroblast growth factor receptor 2 as a novel therapeutic target for colorectal cancer cell growth
Authors: Zenya Naito , Matsuda Yoko , Peng Wei-Xia , Yamahatsu Kazuya , Ueda Junji , Kawamoto Yoko , Teduka Kiyoshi , Seya Tomoko , Ohaki Yoshiharu , Ishiwata Toshiyuki 
Published: June 2012

Background: Colorectal carcinoma (CRC) is one of the most common cancers, and its morbidity is increasing yearly. New therapeutic strategies such as molecular-targeted agents are a high priority for advanced CRC. The multiple alterations in oncogenes and tumor suppressor genes in conjunction with the overexpression of mitogenic or angiogenic growth factors and their receptors, and interaction of the growth factors and receptors contribute to the biological aggressiveness of CRC. A high percentage of CRCs overexpress a number of growth factors and their receptors, including fibroblast growth factor 2 (FGF2), FGF1, fibroblast growth factor receptor 1 (FGFR1) and FGFR2. Recent studies have shown that gene amplification or missence mutation of FGFR2 occurs in gastric cancer, lung cancer, breast cancer, ovarian cancer, endometrial cancer and melanoma. Single nucleotide polymorphisms (SNPs) of FGFR2 are associated with increased risk of breast cancer. Furthermore, inhibition of activated mutation of FGFR2 induced apoptosis and growth inhibition of endometrial carcinoma; therefore, FGFR2 has been considered as a novel therapeutic target for cancers. However, there have been no reports about the inactivation of FGFR2 signaling pathways in CRCs. In this study, we used a silencing strategy to clarify the efficacy of knock down of FGFR2 in human CRC cells. Methods: Immunohistochemical analysis was performed to examine the expression patterns of FGFR2 in human colorectal adenocarcinoma tissues (N=95). Furthermore, FGFR2 short hairpin RNA (shRNA)-transfected CRC cell lines were established from LoVo cells. We have also transfected sham vectors to LoVo cells as negative controls. Cell proliferation, migration, invasion, morphology, and soft agar colony formation assays were performed in FGFR2-shRNA-transfected LoVo cells (Sh) and sham cells (Sc). Results: In CRC cases, FGFR2 immunoreactivity was strongly expressed in cancer cells in the invasive front of cancer tissues. The expression levels of FGFR2 mRNA and protein were low in Sh cells, as compared with Sc cells and wild type cells. Sh cells did not show characteristic morphological alterations as compared to Sc cells. Cell migration and invasion as determined by Boyden chamber assay and time-lapse analysis showed no significant differences between Sh and Sc cells. However, growth rates and colony-forming activities of Sh cells were lower than those of Sc cells in vitro, and tumor volume of subcutaneously implanted Sh cells was low as compared with that of Sc cells in nude mice. Conclusion: These findings suggest that FGFR2 plays important roles in CRC cell growth. FGFR2 may thus serve as a novel therapeutic molecular target for CRCs.

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 1194. doi:10.1158/1538-7445.AM2011-1194