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

Claudio Luparello, Rita Romanotto, Annalisa Tipa, Rosalia Sirchia, Nieves Olmo, Isabel López de Silanes, Javier Turnay, M. Antonia Lizarbe, Andrew F. Stewart

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Parathyroid hormone-related protein (PTHrP) is critical for normal mammary development and is overexpressed by breast cancers. PTHrP is a peptide hormone 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 cancer cell lines "in vitro" and in MDA-MB231 cells "in vivo" specifically examining cell viability, proliferation, invasiveness, and growth in nude mice. PTHrP(38-94)-amide markedly inhibited proliferation and also caused striking 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 growth. These studies (i) indicate breast cancer cells are, one of the few tissues in which specific effects of midregion PTHrP have been established to date, (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.

Original languageEnglish
Pages (from-to)2173-2181
Number of pages9
JournalJournal of Bone and Mineral Research
Volume16
Issue number12
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Cell viability
  • Invasion index
  • Nude mice
  • Parathyroid hormone-related protein 38-94

Fingerprint

Dive into the research topics of 'Midregion parathyroid hormone-related protein inhibits growth and invasion in vitro and tumorigenesis in vivo of human breast cancer cells'. Together they form a unique fingerprint.

Cite this