Fibroblast Growth Factor‐2 Accelerates Invasion of Oral Squamous Cell Carcinoma

Abstract

IntroductionMany recent studies have investigated substances that are involved in the interaction between solid cancer cells and their induced fi broblasts 1 6 . Among them, basic fi broblast growth factor FGF-2 was discovered by Gospodarowicz 7 in 1974 as a protein that strongly promotes the proliferation of fi broblasts. Later studies reported its overexpression in highly malignant cancer cells, and malignant transformation of normal cells transfected with the FGF-2 gene 8,9 . These results suggest that FGF-2 is involved in the invasion of cancer cells and the proliferation of fi broblasts around cancer cells in an autocrine or paracrine fashion ; however, the details are largely unknown.Previously, we reported that in an immunohistochemical study of oral squamous cell carcinoma tissue, the expression or non-expression of FGF-2 in fi broblasts was associated with cancer invasion and metastasis, and the prognosis 10 .In this study, we examined the effects of FGF-2 on cancer cell invasion and on fi broblast proliferation in an in vitro model of invasion.Abstract : The aim of this study was to examine the effects of fi broblast growth factor-2 FGF-2 on cancer cell invasion and on fi broblast proliferation in an in vitro model of invasion. Three kinds of human oral squamous cell carcinoma cell lines with different invasive activity were used : OSC-20, OSC-19 lower invasive type , and HOC313 higher invasive type . FGF-2 and its high-affi nity receptors FGFR-1 and FGFR-2 were detected by western blotting. The expression of FGF-2 and FGFRs mRNA was examined in cultured human oral squamous cell carcinoma cells by reverse transcriptase polymerase chain reaction RT-PCR . Furthermore, recombinant human FGF-2 rhFGF-2 was reacted with each cell line, and the invasion rate was determined by invasion assay. We also observed the behavior of cancer cell invasion in the collagen gel invasion model in the presence or absence of FGF-2-neutralizing antibody anti-FGF-2 . HOC313 cells showed higher expression of FGF-2 than OSC-20 and OSC-19 cells. The addition of rhFGF-2 promoted not only the proliferation of fi broblasts, but also the invasion of all cancer cell lines. In contrast, the addition of anti-FGF-2 completely inhibited the invasion of OSC-20 and OSC-19 cells. These results suggest that a higher invasiveness of squamous carcinoma cells is associated with higher production of FGF-2, which acts in an autocrine fashion to promote cancer cell invasion, and in a paracrine fashion to promote fi broblast proliferation.

Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo

“…It is also important to note that the Matrigel plug model is in fact a better model for assessing cell invasion and invasive migration. This model is commonly used to investigate tumor angiogenesis, mimicking the cancer milieu [25,26]. Moreover, FGF-2 can promote cancer cell invasion [26] and metastasis [27,28].…”

“…This model is commonly used to investigate tumor angiogenesis, mimicking the cancer milieu [25,26]. Moreover, FGF-2 can promote cancer cell invasion [26] and metastasis [27,28]. Whether the cellular infiltration response in vivo induced by TRAIL or FGF-2 is an angiogenic (controlled cellular infiltration) or an invasive response (uncontrolled/aberrant cellular infiltration) is still unclear and requires more investigation.…”

The involvement of fibroblast growth factor receptor signaling pathways in dermatofibroma and dermatofibrosarcoma protuberans

“…We showed strong expressions of FGF2 and FGFR4 in the tumor lesions of DF, while FGF2 and FGFR4 were negative in the tumor lesions of DFSP. FGF2, which is a ligand for all four FGFRs, has been reported to be involved in the invasion of cancer cells and proliferation of fibroblasts around cancer cells in an autocrine or paracrine fashion (25). As for FGFR4, the activation of FGFR4 signaling pathways has been observed in several kinds of cancers including hepatocellular carcinomas, breast cancers, and lung cancers (18).…”

Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells

“…Collagen gels were used as matrices for cancer cell invasion and prepared according to the method of Hase et al (2006) with a little adjustment. Type I collagen (Nippon Meat Packers Inc., Osaka, Japan) was mixed with medium and  10 PBS at a ratio of 1 : 1 : 8 and air-vacuumed for 30 min before incubated in 5% CO 2 and 371C until gelling was completed.…”