卵巢癌细胞与腹膜间皮细胞相互作用对卵巢癌细胞运动及侵袭的影响

Interactions of Ovarian Carcinoma Cells and HPMC Involved in Motility and Invasion of Ovarian Carcinoma to Peritoneum

目的:探讨卵巢癌细胞与腹膜间皮细胞(HPMC)相互作用对卵巢癌细胞运动及侵袭的影响。方法:检测卵巢癌细胞SKOV3条件培养液(CM)及转化生长因子β1(TGF-β1)中和抗体培育HPMC后,HPMC-CM对SKOV3趋化性、趋触性及侵袭性的影响。Checkerboard实验检测HPMC-CM诱导SKOV3运动的方向性。用ELISA检测不同HPMC-CM中纤维粘连蛋白(Fn)及透明质酸(HA)的水平。结果:未刺激组的HPMC-CM1诱导SKOV3趋化、趋触及侵袭(P<0.01)。抗Fn抗体或透明质酸酶(HAase)均可部分抑制HPMC-CM1的作用(P<0.05),二者合用抑制作用增强(P<0.01)。Checkerboard实验证实HPMC-CM1诱导的细胞运动是方向性的。HPMC-CM2Fn及HA蛋白水平高于HPMC-CM1(P<0.01),HPMC-CM3Fn及HA水平较HPMC-CM2降低(P<0.05)。HPMC-CM2诱导趋化、趋触及侵袭的细胞数较HPMC-CM1增多(P<0.01),HPMC-CM3诱导运动及侵袭的细胞数均低于HPMC-CM2(P<0.05)。结论:HPMC合成Fn及HA诱导卵巢癌细胞运动及侵袭,卵巢癌细胞分泌TGF-β1可能通过诱导HPMC合成Fn及HA而促进自身的运动及侵袭。二者相互作用促进卵巢癌的腹膜转移。

Objective： To investigate the interactions of ovarian carcinoma cells and human peritoneal mesothelial cells （HPMC） Involved in motility and invasion of ovarian carcinoma cells to peritoneum. Methods： HPMC were pretreated with ovarian carcinoma cells SKOV3 conditioned medium （CM） in the presence or absence of transforming growth factor β（TGF-β1） neutralizing antibody, and effects of HPMC-CM on chemotaxis, hapotaxis and invasion of SKOV3 were detected. Checkerboard analysis was used to demonstrate whether the induction of motility of SKOV3 by HPMC-CM was diredional. ELISA was used to determine the quantity of fibronectin （Fn） and Hyaluronan （HA） in HPMC-CM. Results： HPMC-CM1 （group without stimulation） induced chemotaxis, hapotaxis and invasion of SKOV3 （P 〈 0.01）, which were partially prevented by either antibody against Fn or hyaluronidase （HAase） （P 〈 0.05）. When both were used together, additive inhibitory effect was observed （P 〈 0.01）. Checkerboard analysis indicated the induced motility of SKOV3 by HPMC-CM1 was directional. The level of Fn and HA in HPMC-CM2 （SKOV3-CM group） increased compared with HPMC-CM1 （P 〈 0.01）. Fn and HA in HPMC-CM3 were less than those in HPMC-CM2 （P 〈 0.05）. SKOV3 showed greater motility and invasion toward HPMC-CM2 than HPMC-CM1 （P 〈 0.01）. Motilityand invasion of SKOV3 toward HPMC-CM3 decreased compared with HPMC-CM2 （P 〈 0.05）. Conclusions： HPMC induce motility and invasion of ovarian carcinoma cells through Fn and HA. Ovarian carcinoma cells furlher promote their own motility and invasion by inducing production of Fn and HA of HPMC through TGF-β1. Interactions of ovarian carcinoma cells and HPMC contribute to peritoneal dissemination of ovarian cancer.