Keratinocyte growth factor binding to fibroblast growth factor receptor 2-IIIb promotes epithelial ovarian cancer cell proliferation and invasion
Jun Wu1, Wei Han2, Weiwei Yang3, Hongyu Liu3, Chunhong Li3, Ling Guo4, Yan Jin5, Ruijie Zhang6, He Chen3
1 Department of Pathology, College of Basic Medicine, Harbin Medical University; Department of Thoracic Surgery Esophageal Mediastinum, Affiliated Tumor Hospital of Harbin Medical University, Harbin 150081, Heilongjiang, China
2 Department of Pathology, Affiliated First Hospital of Harbin Medical University, Harbin 150081, Heilongjiang, China
3 Department of Pathology, College of Basic Medicine, Harbin Medical University, Harbin 150081, Heilongjiang, China
4 Department of Pathology, Affiliated Second Hospital, Mudanjiang Medical College, Mudanjiang 157009, Heilongjiang, China
5 Department of Medical Genetics Key Laboratory of Medical Genetics, Harbin Medical University, Heilongjiang Higher Education Institutions, Harbin 150081, Heilongjiang, China
6 Department of Statistical Genetics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, Heilongjiang, China
Department of Pathology, College of Basic Medicine, Harbin Medical University, Harbin 150081, Heilongjiang
Source of Support: None, Conflict of Interest: None
Aim of Study: To analyze the function of keratinocyte growth factor (KGF) and it ligand fibroblast growth factor receptor 2-IIIb (FGFR2-IIIb) in the epithelial ovarian cancer (EOC) progression.
Materials and Methods: In this study, the protein KGF and corresponding ligand FGFR2-IIIb expression were detected in both normal epithelial ovarian tissues and in EOC tissues. Seventy-one ovarian tumor tissues were examined for KGF and FGFR2-IIIb expression by immunohistochemistry; seven normal epithelial ovarian tissues as control were examined. By using a monoclonal antibody to inhibit KGF activation, we tested KGF-induced EOC cells invasion ability. By means of Western blot, we tested extracellular signal-regulated kinase (ERK), phosphorylation ERK, myosin light chain (MLC), and phosphorylation MLC with or without KGF protein.
Results: We found that the expression FGFR2-IIIb increased in EOC cells and tissues comparing with its normal counterpart, and the expression of KGF protein decreased or undetectable in human EOC cells and tissues comparing with its normal part. The effect of KGF in promoting EOC cell invasion was blocked by an FGFR2-IIIb antibody. We further discovered that KGF upregulated ERK and MLC phosphorylation in the highly invasive ovarian cancer cell line HO8910PM. Therefore, regarding the highly invasive ovarian cancer cells, we speculated that KGF might promote proliferation and invasion through the ERK-MLC pathway.
Conclusions: These results suggest that KGF might play an important role in the progression of ovarian cancer and could be an attractive target for ovarian cancer therapy.