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

Cancer Research - Tập 64 Số 1 - Trang 180-188 - 2004
Thierry Massfelder1, Hervé Lang1, Eric Schordan1, Véronique Lindner1, Sylvie Rothhut1, Sandra Welsch1, Patricia Simon‐Assmann2, Mariette Barthelmebs1, Didier Jacqmin3, Jean‐Jacques Helwig1
11Section of Renovascular Pharmacology and Physiology, Institut National de la Santé et de la Recherche Médicale-University Louis Pasteur, University Louis Pasteur School of Medicine, Strasbourg; Departments of
24Institut National de la Santé et de la Recherche Médicale U381, Strasbourg-Hautepierre, France
32Urology and 3Pathology, University Hospital, Strasbourg; and

Tóm tắt

Abstract 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.

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Cancer Research

Tập 64 Số 1

180-188

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