Abstract
Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression.
Keywords
Adipose derived stem cells
Cell proliferation
Invasion
Matrix metalloproteinases
Ovarian cancer
MeSH Terms
Abdominal Fat/pathology
Adult
Animals
Cell Line, Tumor
Cell Proliferation
Coculture Techniques
Female
Humans
Matrix Metalloproteinase 2/metabolism
Matrix Metalloproteinase 9/metabolism
Mesenchymal Stem Cells/physiology
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Invasiveness
Neoplasm Transplantation
Neoplasms, Glandular and Epithelial/enzymology,secondary
Ovarian Neoplasms/enzymology,pathology
Chemicals
MMP2 protein, human
Matrix Metalloproteinase 2
MMP9 protein, human
Matrix Metalloproteinase 9
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Chu Yijing
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Tang Huijuan
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Guo Yan
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Guo Jing
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Huang Bangxing
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Fang Fang
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China.
Cai Jing
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China. Electronic address: caijingmmm@hotmail.com.
Wang Zehua
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, China. Electronic address: zehuawang@163.net.