Abstract
Adipose-derived stem cells (ADSC) are multipotent mesenchymal stem cells derived from adipose tissues and are capable of differentiating into multiple cell types in the tumor microenvironment (TME). The roles of ADSC in ovarian cancer (OC) metastasis are still not well defined. To understand whether ADSC contributes to ovarian tumor metastasis, we examined epithelial to mesenchymal transition (EMT) markers in OC cells following the treatment of the ADSC-conditioned medium (ADSC-CM). ADSC-CM promotes EMT in OC cells. Functionally, ADSC-CM promotes OC cell proliferation, survival, migration, and invasion. We further demonstrated that ADSC-CM induced EMT via TGF-β growth factor secretion from ADSC and the ensuing activation of the TGF-β pathway. ADSC-CM-induced EMT in OC cells was reversible by the TGF-β inhibitor SB431542 treatment. Using an orthotopic OC mouse model, we also provide the experimental evidence that ADSC contributes to ovarian tumor growth and metastasis by promoting EMT through activating the TGF-β pathway. Taken together, our data indicate that targeting ADSC using the TGF-β inhibitor has the therapeutic potential in blocking the EMT and OC metastasis.
Highlights
Ovarian cancer (OC) is the most lethal gynecological malignancy worldwide, because of its early dissemination in the peritoneal cavity, late detection, and high recurrence rate [1]
We examined cell migration and invasion using the Transwell plates to determine whether Adipose-derived stem cells (ADSC) contribute to OC invasiveness and found that ADSC-conditioned medium (ADSC-conditioned medium (CM)) significantly increased cell migration (Figures 1E, F) and invasion in both OVCAR3 and OVCAR8 cells (Figures 1G, H)
We investigated whether ADSC contributes to OC growth and metastasis by using the transfer of ADSC-CM
Summary
Ovarian cancer (OC) is the most lethal gynecological malignancy worldwide, because of its early dissemination in the peritoneal cavity, late detection, and high recurrence rate [1]. OC metastasizes via pelvic dissemination directly from the primary tumor to peritoneal organs, which is usually asymptomatic at the early stage [2]. MSC has been shown to play different roles in different cancers, including colon, breast, pancreatic, and lung cancer. MSC in the TME have been shown to promote the aggressive malignant phenotypes of various solid cancers, including colon cancer [4] and breast cancer [5]. MSC showed inhibitory effects in lung cancer [6] and liver cancer [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
