Mechanisms of osteoblastic bone metastasis in prostate cancer: Role of prostatic acid phosphatase

Mariana Quiroz-Munoz, Sudeh Izadmehr, Dushyanthy Arumugam, Beatrice Wong, Alexander Kirschenbaum, Alice C. Levine

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Prostate cancer (PCa) preferentially metastasizes to bone, leading to complications including severe pain, fractures, spinal cord compression, bone marrow suppression, and a mortality of;70%. In spite of recent advances in chemo-, hormonal, and radiation therapies, bone-metastatic, castrate-resistant PCa is incurable. PCa is somewhat unique among the solid tumors in its tendency to produce osteoblastic lesions composed of hypermineralized bone with multiple layers of poorly organized type I collagen fibrils that have reduced mechanical strength. Many of the signaling pathways that control normal bone homeostasis are at play in pathologic PCa bone metastases, including the receptor activator of nuclear factor-kB/receptor activator of nuclear factor-kB ligand/osteoprotegerin system. A number of PCa-derived soluble factors have been shown to induce the dysfunctional osteoblastic phenotype. However, therapies directed at these osteoblastic-stimulating proteins have yielded disappointing clinical results to date. One of the soluble factors expressed by PCa cells, particularly in bone metastases, is prostatic acid phosphatase (PAP). Human PAP is a prostate epithelium-specific secretory protein that was the first tumor marker ever described. Biologically, PAP exhibits both phosphatase activity and ecto-50-nucleotidase activity, generating extracellular phosphate and adenosine as the final products. Accumulating evidence indicates that PAP plays a causal role in the osteoblastic phenotype and aberrant bone mineralization seen in bone-metastatic, castrate-resistant PCa. Targeting PAP may represent a therapeutic approach to improve morbidity and mortality from PCa osteoblastic bone metastases.

Original languageEnglish (US)
Pages (from-to)655-664
Number of pages10
JournalJournal of the Endocrine Society
Volume3
Issue number3
DOIs
StatePublished - Mar 2019

Keywords

  • Bone metastases
  • Osteoblastic lesions
  • Osteoblasts
  • Prostate cancer

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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