Exploring the interaction between extracellular matrix components of bone marrow and prostate cancer cells in a novel...

Our study aims to investigate the interaction between disseminated prostate cancer (PC) cells and the extracellular matrix (ECM) of the bone marrow microenvironment (BMM) using a 3Dimensional (3D) in vitro model, which biochemically resembles the stromal ECM part of the hematopoietic stem cell niche. Wharton's Jelly (WJ) was processed and lyophilized to produce a decellularized WJ matrix (DWJM). PC cell lines DU145 and PC-3 were seeded on the DWJM to assess chemosensitivity, cell dormancy, and cancer stemness. CD133, a key marker of PC stem cells (PCSC), was used to evaluate the stemness of the PC cell lines by conventional and imaging flow cytometry. Our results demonstrated that both DU145 and PC-3 cells cultured on DWJM exhibited chemoresistance to Docetaxel and entered a dormant state. Additionally, a small population (~5%) of CD133(+) DU145 cells was detected after 7 days of culture on DWJM. These CD133(+) cells displayed the development of characteristics of epithelial-to-mesenchymal transition. Moreover, limited dilution assay in vivo revealed that DWJM-induced CD133(+) DU145 cells were significantly more tumorigenic than parental DU145 cells. Our findings suggest that PCSCs may be induced in DU145 cells but not in PC-3 cells when PC cells cultured on DWJM.In conclusion, we have developed a 3D in vitro model that effectively mimics the interaction between disseminated PC cells and the ECM of BMM,which may inform the development of therapies targeting metastatic cells in BMM.