title: Human lymphatic endothelial cells contribute to epithelial ovarian carcinoma metastasis by promoting lymphangiogenesis and tumour cell invasion.
abstract: The microenvironment of a tumour is an important factor in ovarian cancer metastasis. The present study aimed to simulate thein vivomicroenvironment of an ovarian carcinoma using a co-culture system consisting of human lymphatic endothelial cells (HLECs) and human ovarian carcinoma cells with directional high lymphatic metastasis (SKOV3-PM4s) in order to investigate the role of both cell types in ovarian carcinoma metastasis. The SKOV3-PM4s cultured in the HLEC-conditioned medium exhibited increased numbers of pseudopodia and mitotic figures, proliferated at a faster rate and exhibited enhanced invasion and migratory abilities. Furthermore, the HLECs cultured in SKOV3-PM4-conditioned medium exhibited significant morphological alterations and vacuolisation of the cytoplasm, as well as increased invasion, migratory and tube forming abilities. In addition, spontaneous fusion of the SKOV3-PM4s and HLECs was observed in the co-culture system using laser confocal microscopy. The gelatin zymography assay demonstrated that matrix metalloproteinase-2, which was downregulated in the SKOV3-PM4s, was upregulated in the co-culture system. The results of the present study suggested that the invasion ability of the SKOV3-PM4s was increased in thein vitroco-culture system of SKOV3-PM4 and HLECs. Therefore, alterations in the cell microenvironment may represent a novel strategy for ovarian cancer therapy.
authors.affiliation: Research Department, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Medical Scientific Research Centre, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Research Department, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Gao
authors.affiliation: Research Department, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Research Department, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: L I
authors.initials: LI
authors.lastname: Li
authors.affiliation: Research Department, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Heyun
authors.initials: H
authors.lastname: Ruan
authors.affiliation: Research Department, Affiliated Tumour Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Danrong
authors.initials: D
authors.lastname: Li
keywords: co-culture; human lymphatic endothelial cells; human ovarian carcinoma cells; lymphangiogenesis; microenvironment