Prostate Cancer Tends To Metastasize In Bone-mimicking Microenvironment Via Activation Of The NF-?B Pathway

Prostate cancer(PCa)preferentially metastasizes to bone resulting in osteoblastic lesions or mixture lesions.However,molecular mechanisms of PCa bone metastasis are still unclear.In current study,we explored the effects of bone microenvironment in PCa cell growth and metastasis.We used osteoblast differentiation medium to mimic bone microenvironment,and then observed whether characteristics alteration of PCa cells in the mimic bone microenvironment,which is MEM Alpha(?-MEM)complete medium supplemented with L-ascorbic acid(AA),compared to those in regular culture medium.Very interestingly,we found that phenotype and properties of PCa cells have been changed significantly when PCa cells grow in the mimic bone microenvironment.The PCa cells occurred EMT,the ability of colony formation increased,as well as the abilities of migration and invasion were enhanced comparing to those cells which grow in regular medium.Using intracardiac injection mouse model,we confirmed all these in vitro findings.Indeed,the ability of metastasis in PCa cells growing in mimic bone microenvironment was enhanced apparently in vivo.Further,we screened several signal pathways related to the invasion and metastasis and found that NF-?B signal pathway was activated,phospho-NF-?B and phospho-I?B? expression were up-regulated,which would be reversed by treating the cells with BAY 11-7082,a NF-?B signal pathway inhibitor.These results shed light on a novel phenomenon that the cells in different culture conditions manifested significant difference biological behaviors.They also suggest that NF-?B signal pathway may be a potential therapeutic target for prostate cancer bone metastasis.