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Platelet-derived Growth Factor D

Tumorigenicity in Mice and Dysregulated Expression in Human Cancer

CuraGen Corp., Branford, Connecticut 06405 [W. J. L., M. J., J. May., J. Mac., B. R., F. W., M. D., J. H., H. S. L.] and Abgenix Inc., Fremont, California 94555 [J. R. F. C., X-C. J., X. F., S. V., J. D. V., X-D. Y., F. C., G. G.]

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer and other proliferative disorders. We have recently isolated and characterized a novel protease-activated member of the PDGF family, PDGF D. PDGF D has been shown to be proliferative for cells of mesenchymal origin, signaling through PDGF receptors. Comprehensive and systematic PDGF D transcript analysis revealed expression in many cell lines derived from ovarian, renal, and lung cancers, as well as from astrocytomas and medulloblastomas. ß PDGF receptor profiling further suggested autocrine signaling in several brain tumor cell lines. PDGF D transforming ability and tumor formation in SCID mice was further demonstrated. Exploiting a sensitive PDGF D sandwich ELISA using fully human monoclonal antibodies, PDGF D was detected at elevated levels in the sera of ovarian, renal, lung, and brain cancer patients. Immunohistochemical analysis confirmed PDGF D localization to ovarian and lung tumor tissues. Together, these data demonstrate that PDGF D plays a role in certain human cancers.

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