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Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases

Authors :
Navatha Shree Polavaram
Samikshan Dutta
Ridwan Islam
Arup K. Bag
Sohini Roy
David Poitz
Jeffrey Karnes
Lorenz C. Hofbauer
Manish Kohli
Brian A. Costello
Raffael Jimenez
Surinder K. Batra
Benjamin A. Teply
Michael H. Muders
Kaustubh Datta
Source :
Bone Research, Vol 9, Iss 1, Pp 1-16 (2021)
Publication Year :
2021
Publisher :
Nature Publishing Group, 2021.

Abstract

Abstract Understanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

Details

Language :
English
ISSN :
20956231
Volume :
9
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Bone Research
Publication Type :
Academic Journal
Accession number :
edsdoj.9a96aa783e4323831a472e68ad3b9d
Document Type :
article
Full Text :
https://doi.org/10.1038/s41413-021-00136-2