Title: Prostate cancer tends to metastasize in bone-mimicking microenvironment via activation of the NF-kB pathway

 

Authors: Haibo Tong1,2, Chunlin Zou1, Siyuan Qin1,2, Jie Meng1,2, Evan T. Keller3, Jian Zhang2,3, Yi Lu1,2

 

Institutions: 1Key Laboratory of Longevity and Aging-related Diseases (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; 2Southern University of Science and Technology School of Medicine, Shenzhen, Guangdong 518055, China; 3Department of Pathology and Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

 

Abstract: Prostate cancer (PCa) preferentially metastasizes to the bone. However, the underlying molecular mechanisms are still unclear. We explored the effects of a bone-mimicking microenvironment on PC3 PCa cell growth and metastasis. We used osteoblast differentiation medium (ODM; minimal essential medium alpha supplemented with L-ascorbic acid) to mimic the bone microenvironment. ODM-grown PC3 cells underwent epithelial-mesenchymal transition (EMT) and showed enhanced colony formation, migration, and invasion abilities as compared to the cells grown in normal medium. PC3 cells grown in ODM showed enhanced metastasis when injected in mice. A screening of several signal pathways related to invasion and metastasis revealed that the NF-kB pathway was activated, which was reversed by treating the cells with Bay 11-7082, a NF-kB pathway inhibitor. These results indicate that the cells in different culture conditions manifested significant difference biological behaviors and suggest that the NF-kB pathway may be a potential therapeutic target for PCa bone metastasis.

 

Keywords: Prostate cancer, metastasis, NF-kB, Bay 11-7082, EMT

 

Full Text: JBR-2018-0035 pre-proof.pdf

 

J Biomed Res published on 01 June 2018, https://doi.org/10.7555/JBR.32.20180035