New concepts of breast cell communication to bone.

Lactation is the most extreme case of normal physiological bone loss during a lifetime, and breast cancers have a strong tendency to metastasize to bone. In both the physiological and pathological circumstances, parathyroid hormone-related peptide (PTHrP) plays a central role. Until recently there were no regulatory mechanisms to explain the induction of endocrine PTHrP secretion from breast cells during lactation. The mammary epithelium possesses a local serotonin signaling system which drives PTHrP expression during lactation and in breast cancer cells. The mammary gland serotonin system is highly induced in response to alveolar dilation due to milk secretion. Discovery of serotonergic control of PTHrP suggests that it may be possible to manipulate the breast-to-bone axis by targeting serotonin signaling.