Platelet-derived growth factor D: tumorigenicity in mice and dysregulated expression in human cancer.
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.
LaRochelle
William J
WJ
CuraGen Corp., Branford, Connecticut 06405, USA. wlarochelle@curagen.com
Jeffers
Michael
M
Corvalan
Jose R F
JR
Jia
Xiao-Chi
XC
Feng
Xiao
X
Vanegas
Sandra
S
Vickroy
Justin D
JD
Yang
Xiao-Dong
XD
Chen
Francine
F
Gazit
Gadi
G
Mayotte
Jane
J
Macaluso
Jennifer
J
Rittman
Beth
B
Wu
Frank
F
Dhanabal
Mohan
M
Herrmann
John
J
Lichenstein
Henri S
HS
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D020797:Receptor, Platelet-Derived Growth Factor beta