Abstract
Malignancies have long been known to markedly alter skeletal and calcium homeostasis. By far the commonest lesion observed in association with most malignancies is skeletal resorption, occasionally accompanied by elevations in blood calcium (hypercalcemia). Osteolysis and hypercalcemia may occur either when the tumor has metastasized to bone, presumably by a paracrine mechanism, or in the absence of skeletal metastases, by an endocrine mechanism. Considerable effort has been expended over the years to attempt to discern the pathogenetic factors involved in these skeletal responses to cancer. This culminated in the isolation of a parathyroid hormone-like peptide (PLP) from cancers, such as renal cancer, which are commonly associated with osteolysis and hypercalcemia [1]. This material is now believed to be the major factor causing hypercalcemia of malignancy. In the human, 3 isoforms of this peptide may exist and this entity is believed now to be a member of aparathyroid hormone/PLP gene family. Currently it is less clear what pathogenetic moieties may act locally in the vicinity of a skeletal metastasis to cause osteolysis. Although prostaglandins of the E series and transforming growth factor alpha (TGFα) have been implicated in this regard, more evidence supports the role of peptide cytokines such as, interleukin-1 and tumor necrosis factor alpha (TNFα) in the local resorption induced by cancer metastases [2].
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Goltzman, D., Bolivar, I., Rabbani, S.A. (1992). Studies on the Pathogenesis of Osteoblastic Metastases by Prostate Cancer. In: Karr, J.P., Yamanaka, H. (eds) Prostate Cancer and Bone Metastasis. Advances in Experimental Medicine and Biology, vol 324. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3398-6_17
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DOI: https://doi.org/10.1007/978-1-4615-3398-6_17
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