Mechanisms of osteolytic bone metastases in breast carcinoma

Sanna Maria Käkönen, Gregory R. Mundy

Research output: Contribution to journalArticlepeer-review

224 Scopus citations

Abstract

Osteolytic and osteoblastic metastases are often the cause of considerable morbidity in patients with advanced prostate and breast carcinoma. Breast carcinoma metastasis to bone occurs because bone provides a favorable site for aggressive behavior of metastatic cancer cells. A vicious cycle arises between cancer cells and the bone microenvironment, which is mediated by the production of growth factors such as transforming growth factor β and insulin growth factor from bone and parathyroid hormone-related protein (PTHrP) produced by tumor cells. Osteolysis and tumor cell accumulation can be interrupted by inhibiting any of these limbs of the vicious cycle. For example, bisphosphonates (e.g., pamidronate, ibandronate, risedronate, clodronate, and zoledronate) inhibit both bone lesions and tumor cell burden in bone in experimental models of breast carcinomametastasis. Neutralizing antibodies to PTHrP, which inhibit PTHrP effects on osteoclastic bone resorption, also reduce osteolytic bone lesions and tumor burden in bone. Other pharmacologic approaches to inhibit PTHrP produced by breast carcinoma cells in the bone microenvironment also produce similar beneficial effects. Identification of the molecular mechanisms responsible for osteolytic metastases is crucial in designing effective therapy for this devastating complication.

Original languageEnglish (US)
Pages (from-to)834-839
Number of pages6
JournalCancer
Volume97
Issue number3 SUPPL.
DOIs
StatePublished - Feb 1 2003

Keywords

  • Bone metastases
  • Breast carcinoma
  • Osteoclasts
  • Osteolysis
  • PTHrP
  • TGFβ

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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