Parathyroid hormone-related protein is an essential growth factor for human clear cell renal carcinoma and a target for the von Hippel-Lindau tumor suppressor gene.
Fiche publication
Date publication
janvier 2004
Auteurs
Membres identifiés du Cancéropôle Est :
Pr JACQMIN Didier, Pr LANG Hervé, Dr LINDNER Véronique, Dr MASSFELDER Thierry
Tous les auteurs :
Massfelder T, Lang H, Schordan E, Lindner V, Rothhut S, Welsch S, Simon-Assmann P, Barthelmebs M, Jacqmin D, Helwig JJ
Lien Pubmed
Résumé
Clear cell renal carcinoma (CCRC) is responsible for 2% of cancer-related deaths worldwide and is resistant to virtually all therapies, indicating the importance of a search for new therapeutic targets. Parathyroid hormone-related protein (PTHrP) is a polyprotein derived from normal and malignant cells that regulates cell growth. In the current study, we show that blocking PTHrP with antibodies or antagonizing the common parathyroid hormone (PTH)/PTHrP receptor, the PTH1 receptor, dramatically blunts the expansion of human CCRC in vitro by promoting cell death. Importantly, in nude mice, anti-PTHrP antibodies induced complete regression of 70% of the implanted tumors by inducing cell death. In addition, we demonstrate that the von Hippel-Lindau tumor suppressor protein, which functions as a gatekeeper for CCRC, negatively regulates PTHrP expression at the post-transcriptional level. These studies indicate that PTHrP is an essential growth factor for CCRC and is a novel target for the von Hippel-Lindau tumor suppressor protein. Taken together, these results strongly suggest that targeting the PTHrP/PTH1 receptor system may provide a new avenue for the treatment of this aggressive cancer in humans.
Référence
Cancer Res. 2004 Jan 1;64(1):180-8.