The sequence similarity within the amino-terminal regions of
parathyroid hormone (PTH) and PTH-related
protein (
PTHrP) allows the two to share actions at a common site, the PTH1 receptor. A number of
biological activities have been ascribed to actions of other domains within
PTHrP.
PTHrP production by late stage
breast cancer has been shown to contribute to bone
metastasis formation through promotion of osteoclast formation and
bone resorption by action through PTH1 receptors. There is evidence also for a role for
PTHrP early in
breast cancer that is protective against tumour progression. No signalling pathway has been identified for this effect.
PTHrP has also been identified as
a factor promoting the emergence of
breast cancer cells from dormancy in bone. In that case,
PTHrP does not function through activation of PTH1 receptors, despite having very substantial effects on transcriptional activity of the
breast cancer cells. This indicates actions of
PTHrP that are non-canonical, that is, mediated through domains other than the amino-terminal. It is concluded that
PTHrP has several distinct paracrine, autocrine, and intracrine actions in the course of
breast cancer pathophysiology. Some are mediated through action at PTH1 receptors and others are controlled by other domains within
PTHrP. LINKED ARTICLES: This article is part of a themed issue on The molecular pharmacology of bone and
cancer-related
bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc.