GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation.

ABSTRACT: Bone metastases occur in patients with advanced-stage prostate cancer (PCa). The cell-cell interaction between PCa and the bone microenvironment forms a vicious cycle that modulates the bone microenvironment, increases bone deformities, and drives tumor growth in the bone. However, the molecular mechanisms of PCa-mediated modulation of the bone microenvironment are complex and remain poorly defined. Here, we evaluated growth differentiation factor-15 (GDF15) function using in vivo preclinical PCa-bone metastasis mouse models and an in vitro bone cell coculture system. Our results suggest that PCa-secreted GDF15 promotes bone metastases and induces bone microarchitectural alterations in a preclinical xenograft model. Mechanistic studies revealed that GDF15 increases osteoblast function and

SUBMITTER: Siddiqui JA 

PROVIDER: S-EPMC8776828 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature