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Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone.
Endocr Relat Cancer. 2005 Sep; 12(3):549-83.ER

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-beta 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.

Authors+Show Affiliations

Clines GA
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, PO Box 801419, Charlottesville, Virginia 22908-1419, USA.
Guise TA
No affiliation info available

MeSH

Bone NeoplasmsDiphosphonatesHumansHypercalcemiaMuscle NeoplasmsNeoplasm MetastasisNeoplasmsOsteoblastsOsteolysisResearch Design

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

16172192

Citation

Clines, G A., and T A. Guise. "Hypercalcaemia of Malignancy and Basic Research On Mechanisms Responsible for Osteolytic and Osteoblastic Metastasis to Bone." Endocrine-related Cancer, vol. 12, no. 3, 2005, pp. 549-83.
Clines GA, Guise TA. Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endocr Relat Cancer. 2005;12(3):549-83.
Clines, G. A., & Guise, T. A. (2005). Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. Endocrine-related Cancer, 12(3), 549-83.
Clines GA, Guise TA. Hypercalcaemia of Malignancy and Basic Research On Mechanisms Responsible for Osteolytic and Osteoblastic Metastasis to Bone. Endocr Relat Cancer. 2005;12(3):549-83. PubMed PMID: 16172192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone. AU - Clines,G A, AU - Guise,T A, PY - 2005/9/21/pubmed PY - 2005/11/16/medline PY - 2005/9/21/entrez SP - 549 EP - 83 JF - Endocrine-related cancer JO - Endocr Relat Cancer VL - 12 IS - 3 N2 - 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-beta 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. SN - 1351-0088 UR - https://www.unboundmedicine.com/medline/citation/16172192/Hypercalcaemia_of_malignancy_and_basic_research_on_mechanisms_responsible_for_osteolytic_and_osteoblastic_metastasis_to_bone_ DB - PRIME DP - Unbound Medicine ER -