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

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 mec...

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Autores principales: Siddiqui, Jawed Akhtar, Seshacharyulu, Parthasarathy, Muniyan, Sakthivel, Pothuraju, Ramesh, Khan, Parvez, Vengoji, Raghupathy, Chaudhary, Sanjib, Maurya, Shailendra Kumar, Lele, Subodh Mukund, Jain, Maneesh, Datta, Kaustubh, Nasser, Mohd Wasim, Batra, Surinder Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776828/
https://www.ncbi.nlm.nih.gov/pubmed/35058441
http://dx.doi.org/10.1038/s41413-021-00178-6
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author Siddiqui, Jawed Akhtar
Seshacharyulu, Parthasarathy
Muniyan, Sakthivel
Pothuraju, Ramesh
Khan, Parvez
Vengoji, Raghupathy
Chaudhary, Sanjib
Maurya, Shailendra Kumar
Lele, Subodh Mukund
Jain, Maneesh
Datta, Kaustubh
Nasser, Mohd Wasim
Batra, Surinder Kumar
author_facet Siddiqui, Jawed Akhtar
Seshacharyulu, Parthasarathy
Muniyan, Sakthivel
Pothuraju, Ramesh
Khan, Parvez
Vengoji, Raghupathy
Chaudhary, Sanjib
Maurya, Shailendra Kumar
Lele, Subodh Mukund
Jain, Maneesh
Datta, Kaustubh
Nasser, Mohd Wasim
Batra, Surinder Kumar
author_sort Siddiqui, Jawed Akhtar
collection PubMed
description 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.
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spelling pubmed-87768282022-02-04 GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation Siddiqui, Jawed Akhtar Seshacharyulu, Parthasarathy Muniyan, Sakthivel Pothuraju, Ramesh Khan, Parvez Vengoji, Raghupathy Chaudhary, Sanjib Maurya, Shailendra Kumar Lele, Subodh Mukund Jain, Maneesh Datta, Kaustubh Nasser, Mohd Wasim Batra, Surinder Kumar Bone Res Article 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. Nature Publishing Group UK 2022-01-20 /pmc/articles/PMC8776828/ /pubmed/35058441 http://dx.doi.org/10.1038/s41413-021-00178-6 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Siddiqui, Jawed Akhtar
Seshacharyulu, Parthasarathy
Muniyan, Sakthivel
Pothuraju, Ramesh
Khan, Parvez
Vengoji, Raghupathy
Chaudhary, Sanjib
Maurya, Shailendra Kumar
Lele, Subodh Mukund
Jain, Maneesh
Datta, Kaustubh
Nasser, Mohd Wasim
Batra, Surinder Kumar
GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation
title GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation
title_full GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation
title_fullStr GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation
title_full_unstemmed GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation
title_short GDF15 promotes prostate cancer bone metastasis and colonization through osteoblastic CCL2 and RANKL activation
title_sort gdf15 promotes prostate cancer bone metastasis and colonization through osteoblastic ccl2 and rankl activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776828/
https://www.ncbi.nlm.nih.gov/pubmed/35058441
http://dx.doi.org/10.1038/s41413-021-00178-6
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