Delineating role of NF‐κB and interacting cytokines during prostate cancer‐induced osteoclastogenesis. Issue 2 (14th October 2020)

• Record Type: Journal Article
• Authors: Jadli, Mohit; Thakur, Kulbhushan; Aggarwal, Nikita; Chhokar, Arun; Bibban, Rakhi; Singh, Tejveer; Bhat, Anjali; Bharti, Alok C.
• Is Part Of: Journal of cellular biochemistry. Volume 122:Issue 2(2021)
• Page Start: 259
• Page End: 276
• Publication Date: 2020-10-14
• Subjects: IL‐6 -- NF‐κB -- osteoclast -- prostate cancer -- RANKL -- TNF‐α; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29856
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Prostate cancer (PCa) frequently metastasizes to the bone leading to devastating complications such as severe pain and fracture. However, the mechanisms by which PCa cells cause bone loss remain less understood. We investigated the role and mechanisms by which PCa cells induce osteoclastogenesis using cultured monocytic osteoclast precursors. Treatment of RAW264.7 cells with PCa cell lines: DU145, LNCaP, PC‐3, or their conditioned media led to the formation of distinct multinucleated, TRAP + osteoclasts. This phenomenon was associated with the increased activation of transcription factor nuclear factor‐k B (NF‐κB). High transcript level of receptor activator of nuclear factor‐k B ligand (RANKL), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) were detected in PCa cells. TNF‐α and LT‐α augmented, whereas IL‐6 reduced the RANKL‐induced osteoclast formation in RAW264.7 cultures. Our results also demonstrated that PCa cells‐induced osteoclastogenesis involved the activation of the TRAF6–IKK–p65–NF‐κB signaling cascade. Together, our study demonstrates that PCa cells produce RANKL and several other pro‐inflammatory cytokines known to influence osteoclastogenesis, by targeting the NF‐κB signaling pathway. Abstract : Prostate cancer (PCa) has high propensity for bone metastasis through osteoclastogenesis. Our data show canonical receptor activator of nuclear factor‐k B ligand, and other noncanonical cytokines, tumor necrosis factor‐α and interleukin‐6, released by PCa cells collectively regulate this process. The osteoclastic capability of PCa cells is mediated via nuclear factor‐k B (NF‐k B). Blocking NF‐k B abrogates PCa‐induced osteoclast development and differentiation.