Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

G. A. Clines, Theresa Guise

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the 'seed and soil' hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-β that further stimulates local cancer cells. This Vicious cycle' of bone metastases represents reciprocal bone/cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the Vicious cycle' is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.

Original languageEnglish (US)
Pages (from-to)549-583
Number of pages35
JournalEndocrine-Related Cancer
Volume12
Issue number3
DOIs
StatePublished - Sep 2005
Externally publishedYes

Fingerprint

Hypercalcemia
Neoplasm Metastasis
Bone and Bones
Bone Neoplasms
Research
Neoplasms
Parathyroid Hormone-Related Protein
Homeostasis
Parathyroid Glands
Bone Diseases
Diphosphonates
Transforming Growth Factors
Osteoclasts
Chemotaxis
Bone Resorption
Skeleton
Intestines
Lung Neoplasms
Seeds
Soil

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. / Clines, G. A.; Guise, Theresa.

In: Endocrine-Related Cancer, Vol. 12, No. 3, 09.2005, p. 549-583.

Research output: Contribution to journalArticle

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