Midregion parathyroid hormone-related protein inhibits growth and invasionin vitro and tumorigenesis in vivo of human breast cancer cells

Parathyroid hormone-related protein (PTHrP) is critical for normal mammary development and is overexpressed by breast cancers. PTHrP is a peptide horm one that undergoes extensive post-translational processing, and PTHrP(38-94 )-amide is one of the mature secretory forms of the peptide. In this study, we explored the effect of PTHrP(38-94)-amide in a panel of six breast canc er cell lines "in vitro" and in MDA-MB231 cells "in vivo" specifically exam ining cell viability, proliferation, invasiveness, and growth in nude mice. PTHrP(38-94)-amide markedly inhibited proliferation and also caused striki ng toxicity and accelerated cell death in breast cancer cells. In addition, direct injection of PTHrP(38-94)-amide into MDA-MB231 breast cancer cells passaged in immunodeficient mice produced a marked reduction in tumor growt h. These studies (i) indicate breast cancer cells are one of the few tissue s in which specific effects of midregion PTHrP have been established to dat e, (ii) support a role for midregion secretory forms of PTHrP in modulating not only normal but also pathological mammary growth and differentiation, (iii) add further evidence for the existence of a specific midregion PTHrP receptor, and (iv) provide a novel molecule for modeling of small molecule analogues that may have anti-breast cancer effects.