Resumen de DT‑13 inhibits breast cancer cell migration via non‑muscle myosin II‑A regulation in tumor microenvironment synchronized adaptation
Y. Gao, G.J. Khan, X. Wei, K.F. Zhai, L. Sun, S. Yuan
Background Tumor metastasis is a terrifying characteristic of cancer. Numerous studies have been conducted to overcome metastasis by targeting tumor microenvironment (TME). However, due to complexity of tumor microenvironment, it remained difficult for accurate targeting. Dwarf-lillytruf tuber monomer-13 (DT-13) possess good potential against TME.
Objective As TME is supportive for tumor metastasis, alternatively it is a challenging for therapeutic intervention. In our present study, we explored molecular mechanism through which TME induced cell migration and how DT-13 interferes in this mechanism.
Methods We used a novel model of co-culture system which is eventually developed in our lab. Tumor cells were co-cultured with hypoxia induced cancer-associated fibroblasts (CAF) or with chemically induced cancer-associated adipocytes (CAA).
The effect of hypoxia in conditioned medium for CAF was assessed through expression of α-SMA and HIF by western blot- ting while oil red staining was done to assess the successful chemical induction for adipocytes (CAA), the effect of TME through conditioned medium on cell migration was analyzed by trans-well cell migration, and cell motility (wound healing) analyses. The expression changes in cellular proteins were assessed through western blotting and immunofluorescent studies.
Results and conclusion Our results showed that tumor microenvironment has a direct role in promoting breast cancer cell migration by stromal cells; moreover, we found that DT-13 restricts this TME regulated cell migration via targeting stromal cells in vitro. Additionally we also found that DT-13 targets NMII-A for its effect on breast cancer cell migration for the regulation of stromal cells in TME
