Structural Basis for Antibody Discrimination between Two Hormones That Recognize the Parathyroid Hormone Receptor
William J McKinstry, Galina Polekhina, Hannelore Diefenbach-Jagger, Patricia WM Ho, Koh Sato, Etsuro Onuma, Matthew T Gillespie, T John Martin, Michael W Parker
JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2009
Parathyroid hormone-related protein (PTHrP) plays a vital role in the embryonic development of the skeleton and other tissues. When it is produced in excess by cancers it can cause hypercalcemia, and its local production by breast cancer cells has been implicated in the pathogenesis of bone metastasis formation in that disease. Antibodies have been developed that neutralize the action of PTHrP through its receptor, parathyroid hormone receptor 1, without influencing parathyroid hormone action through the same receptor. Such neutralizing antibodies against PTHrP are therapeutically effective in animal models of the humoral hypercalcemia of malignancy and of bone metastasis formation. We have ..View full abstract
This work was supported in part by grants from the Cancer Council of Victoria and National Health and Medical Research Council of Australia with infrastructural support from the Australian Cancer Research Foundation Rational Drug Discovery Facility. This work, including use of the BioCARS sector, was also supported by the Australian Synchrotron Research Program, which is funded by the Commonwealth of Australia. Use of the Advanced Photon Source was supported by the United States Department of Energy, Basic Energy Sciences, Office of Energy Research.