Osteoblastic Factors in Prostate Cancer Bone Metastasis
Purpose of Review
Prostate cancer bone metastasis is the lethal progression of the disease. The disease frequently presents with osteoblastic lesions in bone. The tumor-induced bone can cause complications that significantly hamper the quality of life of patients. A better understanding of how prostate cancer induces aberrant bone formation and how the aberrant bone affects the progression and treatment of the disease may improve the therapies for this disease.
Prostate cancer-induced bone was shown to enhance tumor growth and confer therapeutic resistance in bone metastasis. Clinically, Radium-223, an alpha emitter that selectively targets bone, was shown to improve overall survival in patients, supporting a role of tumor-induced bone in prostate cancer progression in bone. Recently, it was discovered that PCa-induced aberrant bone formation is due, in part, from tumor-associated endothelial cells that were converted into osteoblasts through endothelial-to-osteoblast (EC-to-OSB) conversion by tumor-secreted BMP4.
The unique bone-forming phenotype of prostate cancer bone metastasis plays a role in prostate cancer progression in bone and therapy resistance. Therapies that incorporate targeting the tumor-induced osteoblasts or EC-to-OSB conversion mechanism may reduce tumor-induced bone formation and improve therapy outcomes.
KeywordsBone metastasis Prostate cancer Tumor-induced bone Osteocrines EC-to-OSB conversion
This work was supported by grants from the NIH R01CA174798, NIH 5P50CA140388, NIH P30CA16672 Core grant to M.D. Anderson Cancer Center; Cancer Prevention Research Institute of Texas CPRIT RP150179; and Sister Institute Network Fund at U. Texas M.D. Anderson Cancer Center.
Compliance with Ethical Standards
All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki Declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).
Conflict of Interest
Song-Chang Lin, Li-Yuan Yu-Lee, and Sue-Hwa Lin declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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