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

Jawed Akhtar Siddiqui, Parthasarathy Seshacharyulu, Sakthivel Muniyan, Ramesh Pothuraju, Parvez Khan, Raghupathy Vengoji, Sanjib Chaudhary, Shailendra Kumar Maurya, Subodh Mukund Lele, Maneesh Jain, Kaustubh Datta, Mohd Wasim Nasser, Surinder Kumar Batra

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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 facilitates the growth of PCa in bone by activating osteoclastogenesis through osteoblastic production of CCL2 and RANKL and recruitment of osteomacs. Altogether, our findings demonstrate the critical role of GDF15 in the modulation of the bone microenvironment and subsequent development of PCa bone metastasis.

Original languageEnglish (US)
Article number6
JournalBone Research
Volume10
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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