Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases.
Journal
Bone research
ISSN: 2095-4700
Titre abrégé: Bone Res
Pays: China
ID NLM: 101608652
Informations de publication
Date de publication:
14 May 2021
14 May 2021
Historique:
received:
14
05
2020
accepted:
26
11
2020
revised:
22
10
2020
entrez:
15
5
2021
pubmed:
16
5
2021
medline:
16
5
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33990538
doi: 10.1038/s41413-021-00136-2
pii: 10.1038/s41413-021-00136-2
pmc: PMC8121836
doi:
Types de publication
Journal Article
Langues
eng
Pagination
24Subventions
Organisme : NCI NIH HHS
ID : R01 CA182435
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239343
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA241234
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA185148
Pays : United States
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