Nakamura Michihiko, Ono Yoshihiro J, Kanemura Masanori, Tanaka Tomohito, Hayashi Masami, Terai Yoshito, Ohmichi Masahide
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 5650781, Japan.
Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka 5650781, Japan.
Gynecol Oncol. 2015 Nov;139(2):345-54. doi: 10.1016/j.ygyno.2015.08.010. Epub 2015 Aug 31.
A current working model for the metastatic process of ovarian carcinoma suggests that cancer cells are shed from the ovarian tumor into the peritoneal cavity and attach to the layer of mesothelial cells that line the inner surface of the peritoneum, and several studies suggest that hepatocyte growth factor (HGF) plays an important role in the dissemination of ovarian cancer. Our objectives were to evaluate the HGF expression of ovarian cancer using clinical data and assess the effect of HGF secreted from human ovarian cancer cells to human mesothelial cells.
HGF expression was immunohistochemically evaluated in 165 epithelial ovarian cancer patients arranged as tissue microarrays. HGF expression in four ovarian cancer cell lines was evaluated by using semi-quantitative polymerase chain reaction, Western blotting and enzyme-linked immunosorbent assay. The effect of ovarian cancer cell derived HGF to the human mesothelial cells was assessed by using morphologic analysis, Western blotting and cell invasion assay. The effect of HGF on ovarian cancer metastasis was assessed by using in vivo experimental model.
The clinical data showed a significantly high correlation between the HGF expression and the cancer stage. The in vivo and in vitro experimental models revealed that HGF secreted by ovarian cancer cells induces the mesothelial-to-mesenchymal transition and stimulates the invasion of mesothelial cells. Furthermore, manipulating the HGF activity affected the degree of dissemination and ascite formation.
We demonstrated that HGF secreted by ovarian cancer cells plays an important role in cancer peritoneal implantation.
目前关于卵巢癌转移过程的工作模型表明，癌细胞从卵巢肿瘤脱落进入腹腔，并附着于覆盖腹膜内表面的间皮细胞层，多项研究表明肝细胞生长因子（HGF）在卵巢癌播散中起重要作用。我们的目的是利用临床数据评估卵巢癌中HGF的表达，并评估人卵巢癌细胞分泌的HGF对人间皮细胞的影响。
采用免疫组织化学方法对165例上皮性卵巢癌患者组织芯片中的HGF表达进行评估。采用半定量聚合酶链反应、蛋白质免疫印迹法和酶联免疫吸附测定法评估四种卵巢癌细胞系中HGF的表达。通过形态学分析、蛋白质免疫印迹法和细胞侵袭试验评估卵巢癌细胞来源的HGF对人间皮细胞的影响。采用体内实验模型评估HGF对卵巢癌转移的影响。
临床数据显示HGF表达与癌症分期之间存在显著的高度相关性。体内和体外实验模型表明，卵巢癌细胞分泌的HGF诱导间皮-间充质转化并刺激间皮细胞的侵袭。此外，操纵HGF活性会影响播散程度和腹水形成。
我们证明卵巢癌细胞分泌的HGF在癌症腹膜种植中起重要作用。
