Wu Jun, Han Wei, Yang Weiwei, Liu Hongyu, Li Chunhong, Guo Ling, Jin Yan, Zhang Ruijie, Chen He
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.
Department of Pathology, Affiliated First Hospital of Harbin Medical University, Harbin 150081, Heilongjiang, China.
J Cancer Res Ther. 2018 Jun;14(Supplement):S347-S353. doi: 10.4103/0973-1482.235353.
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.
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.
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.
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.
分析角质形成细胞生长因子（KGF）及其配体成纤维细胞生长因子受体2-IIIb（FGFR2-IIIb）在上皮性卵巢癌（EOC）进展中的作用。
在本研究中，检测了正常上皮性卵巢组织和EOC组织中KGF蛋白及其相应配体FGFR2-IIIb的表达。通过免疫组织化学检测了71例卵巢肿瘤组织中KGF和FGFR2-IIIb的表达；检测了7例正常上皮性卵巢组织作为对照。通过使用单克隆抗体抑制KGF激活，我们测试了KGF诱导的EOC细胞侵袭能力。通过蛋白质印迹法，我们检测了有无KGF蛋白时细胞外信号调节激酶（ERK）、磷酸化ERK、肌球蛋白轻链（MLC）和磷酸化MLC的情况。
我们发现，与正常对应物相比，EOC细胞和组织中FGFR2-IIIb的表达增加，而与正常部分相比，人EOC细胞和组织中KGF蛋白的表达降低或无法检测到。FGFR2-IIIb抗体阻断了KGF促进EOC细胞侵袭的作用。我们进一步发现，KGF上调了高侵袭性卵巢癌细胞系HO8910PM中ERK和MLC的磷酸化。因此，对于高侵袭性卵巢癌细胞，我们推测KGF可能通过ERK-MLC途径促进增殖和侵袭。
这些结果表明，KGF可能在卵巢癌进展中起重要作用，并且可能成为卵巢癌治疗的一个有吸引力的靶点。
