Platelet-derived growth factor D: Tumorigenicity in mice and dysregulated expression in human cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 9; pp. 2468 - 2473
• Main Authors: LAROCHELLE, William J, JEFFERS, Michael, MAYOTTE, Jane, MACALUSO, Jennifer, RITTMAN, Beth, WU, Frank, DHANABAL, Mohan, HERRMANN, John, LICHENSTEIN, Henri S, CORVALAN, Jose R. F, JIA, Xiao-Chi, XIAO FENG, VANEGAS, Sandra, VICKROY, Justin D, YANG, Xiao-Dong, CHEN, Francine, GAZIT, Gadi
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-05-2002
• Subjects: 3T3 Cells; Animals; Biological and medical sciences; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry; Medical sciences; Mice; Mice, SCID; Molecular and cellular biology; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasms - blood; Neoplasms - metabolism; Neoplasms - pathology; Phosphorylation; Platelet-Derived Growth Factor - biosynthesis; Platelet-Derived Growth Factor - genetics; Platelet-Derived Growth Factor - physiology; Receptor, Platelet-Derived Growth Factor beta - metabolism; Receptor, Platelet-Derived Growth Factor beta - physiology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal Transduction - physiology; Tumor Cells, Cultured; Tumors; Human; Tumoral tissue; Rodentia; Gene overexpression; Tumorigenicity; Malignant tumor; Gene expression; In vitro; Vertebrata; Mammalia; Mouse; Animal; Mechanism of action; Platelet derived growth factor
• ISSN: 0008-5472; 1538-7445

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. beta 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.