Expression of keratinocyte growth factor receptor correlates with expansive growth and early stage of gastric cancer

Abstract

Abstract. The keratinocyte growth factor receptor, also known as KGFR/FGFR2 IIIb, is mainly localized in epithelial cells, and participates in the proliferation of these cells. In contrast, a recent study has revealed that the overexpression of KGFR in salivary adenocarcinoma induces growth inhibition, cell differentiation and apoptosis. We attempted to clarify the expression and role of KGFR in normal and cancerous human gastric tissues and cancer cell lines. Reverse-transcription polymerase chain reaction and Western blot analyses showed KGFR mRNA and its protein expression in NUGC-4, KATO-III and MKN-7 gastric cancer cell lines, but not in the NS-8 cell line. Immunohistochemically, KGFR immunoreactivity was weakly detected in the luminal surface of normal gastric epithelial cells. In addition, KGFR immunoreactivity was strongly detected in the nucleus and cytoplasm of many parietal cells. In gastric cancer tissue, KGFR was expressed in the cell membrane and cytoplasm of cancer cells in 46 of 126 (36.5%) cases. KGFR expression in gastric cancer cells was significantly associated with early-type macroscopic findings, shallow invasion of the gastric wall and expansive growth type. KGFR expression tended to correlate with a good prognosis in gastric cancer. These findings indicate that KGFR expression plays important roles in the differentiation of normal gastric epithelial cells and parietal cell functions. Furthermore, a decreased expression level or the non-expression of KGFR in gastric cancer cells may be associated with the proliferation and invasion of gastric cancer cells and a poor prognosis for the patient.

Expression and roles of keratinocyte growth factor and its receptor in esophageal cancer cells

“…In this study, we found that, in noncancerous esophageal tissues, KGFR is localized in the lower one-third of squamous epithelial cells and its localization is broader than that of Ki-67, a proliferating cell marker. In gastric and colorectal tissues, KGFR is localized in the luminal surface of epithelial cells, but Ki-67 is localized in the nuclei of ductal cells in the basal and parabasal regions (14,27). These findings suggest that KGFR plays important roles not only in epithelial cell proliferation in the GI tract, but also in cell differentiation.…”

“…We previously reported the KGFR expression in cancer cell lines derived from the GI tract, including the esophagus, stomach and colon (14,27). Conventional gastric cancer cell lines expressed KGFR, but special types of gastric cancer cell line from metastatic foci of adenosquamous cells and α-fetoprotein-producing gastric cancer cells did not express KGFR (27,29).…”

“…Conventional gastric cancer cell lines expressed KGFR, but special types of gastric cancer cell line from metastatic foci of adenosquamous cells and α-fetoprotein-producing gastric cancer cells did not express KGFR (27,29). In colorectal cancer cell lines, KGFR was strongly expressed in cancer cells originating from welldifferentiated adenocarcinoma (14).…”

“…The sections were lightly counterstained with Mayer's hematoxylin. Positivity for KGFR and KGF was classified according to the percentage of positive tumor cells regardless of staining intensities: when KGFR staining was observed in the cytoplasm or membrane of >10% of the tumor cells, the patients were designated KGFR-positive (26,27); when KGF staining was observed in the cytoplasm of >30% of the tumor cells, the patients were designated KGF-positive (28). Two investigators (M.Y.…”

A Novel, Selective Inhibitor of Fibroblast Growth Factor Receptors That Shows a Potent Broad Spectrum of Antitumor Activity in Several Tumor Xenograft Models

“…FGFR and FGF are often overexpressed in numerous cancers, and their expression correlates with poor prognosis (7)(8)(9)(10)(11)(12)(13). Activating mutations in the FGFR kinase domain have been found in several types of tumors including breast, bladder, gastric, prostate, colon, multiple myeloma, and non-small cell lung carcinoma (NSCLC; refs.…”