Title: Prostate cancer tends to metastasize in the bone-mimicking microenvironment via activating NF-kB signaling


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


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


Full Text: JBR-2018-0035.pdf


J Biomed Res published on 26 July 2018, https://doi.org/10.7555/JBR.32.20180035