Introduction:

Prostate cancer (PCa) is a leading cause of cancer-related deaths in men, with bone metastasis significantly contributing to morbidity and mortality. The bone microenvironment is a fertile "soil" for metastatic "seeds." Understanding the molecular mechanisms governing PCa bone metastasis is crucial for developing effective therapies. This study investigates the role of FOXI3, a member of the Forkhead-box (FOX) family of transcription factors, in PCa bone metastasis. While the functions of some FOX proteins in cancer are well-established, the specific role of FOXI3 in PCa remains largely unexplored. Recent studies suggest FOXI3 is involved in bone development and homeostasis.

Methods:

An indirect co-culture experiment using a transwell plate will be used to examine the interaction between PCa cells and bone marrow stromal cells. PCa cell lines will be seeded in the bottom chambers of 6-well plates (100,000 cells/well, 2mL media). Bone marrow stromal cells will be cultured in upper chambers (100,000 cells/1mL media). After a 24 and 48-hour co-culturing, gene expression will be assessed using RT-PCR and qRT-PCR for FOXI3. Protein analysis will be measured using Western blot. Additionally, we will repeat co-culturing and investigate the effects of bone-derived factors (FGF8 and TGF-β) on FOXI3 expression and PCa cell behavior.

Results:

As this is a research proposal, results are pending. We anticipate exposure to bone marrow stromal cell-conditioned media will increase FOXI3 expression and other pro-tumorigenic factors in PCa cells. We expect that FOXI3 removal will reduce prostate cells' invasive and metastatic potential in the simulated bone microenvironment.

Conclusion:

This research aims to elucidate the interplay between FOXI3 and the bone microenvironment, potentially uncovering new therapeutic targets for PCa bone metastasis. Understanding these mechanisms could lead to improved treatment strategies and better outcomes for patients with advanced prostate cancer.