Mesenchymal stem cells in inflammatory microenvironment promotes cancer cell migration and epithelialmesenchymal transition through osteopontin

Global Summit on Oncology & Cancer

May 25-27, 2017 Osaka, Japan

Tzu-Ching Chang and Chia-Cherng Yu

China Medical University, Taiwan
National Taiwan University Hospital, Taiwan

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

Backgrounds: Mesenchymal stem cells (MSCs) provide potential regenerative effects on chronic kidney disease (CKD) due to their paracrine signaling with cell tropic and anti-inflammation properties. However, in CKD patients combined with renal cell carcinoma (RCC), the roles of MSCs in inflammatory or tumorsâ�� microenvironment are still controversial. Methods & Results: To evaluate the real characteristics of MSCs in inflammatory microenvironment, we first detected the human MSC secretome by cytokine array after MSCs were incubated with or without inflammatory cytokines (IL-1�² or TNF-�±). The array data showed that, compared to control MSCs, osteopontin (OPN) were significantly increased after MSCs were incubated with inflammatory cytokines. Furthermore, OPN mRNA level and protein secretion were confirmed by quantitative real-time PCR and ELISA respectively. We further collected MSC condition medium (MSC-CM) after inflammatory cytokine treatments to test the effects of MSC-CM as well as OPN alone on RCC migration. MSC-CM and OPN alone facilitated RCC migration by Boydon chamber assay. The epithelial-mesenchymal transition (EMT) of RCC was significantly promoted by MSC-CM and OPN alone since the reduction of E-cadherin and increase of Snail and vimentin. Using OPN-specific antibody to neutralize OPN in MSC-CM would attenuate the RCC migration and EMT that were stimulated by whole MSC-CM. Moreover, the activities of cancer-associated fibroblasts (CAF) were enhanced by treating CAF with MSC-CM and OPN alone. Conclusion & Significance: In this study, we demonstrated that OPN secreted by MSCs would promote cancer cell migration, EMT progression and CAF activation while MSCs were incubated in an inflammatory microenvironment. We hope that this study will provide another consideration of MSC application in kidney regeneration while CKD patients combined with RCC.

Biography :

Tzu-Ching Chang has completed her PhD from Graduate Institute of Life Science, National Defense Medical Center, Taiwan. She did her Master’s degree from Institute of Physiology, National Taiwan University, College of Medicine, Taiwan. Her areas of research include Molecular Cell Biology, Stem Cell Biology and Cancer Cell Biology.

Email: ctching9@gmail.com