Neuropilin-1 expression by tumor cells promotes tumor angiogenesis and progression.
Neuropilin-1 (NRP1) is a VEGF(165) and semaphorin receptor expressed by vascular endothelial cells (EC) and tumor cells. The function of NRP1 in tumor cells is unknown. NRP1 was overexpressed in Dunning rat prostate carcinoma AT2.1 cells using a tetracycline-inducible promoter. Concomitant with increased NRP1 expression in response to a tetracycline homologue, doxycycline (Dox), basal cell motility, and VEGF(165) binding were increased three- to fourfold in vitro. However, induction of NRP1 did not affect tumor cell proliferation. When rats injected with AT2.1/NRP1 tumor cells were fed Dox, NRP1 synthesis was induced in vivo and AT2.1 cell tumor size was increased 2.5- to 7-fold in a 3-4 wk period compared to controls. The larger tumors with induced NRP1 expression were characterized by markedly increased microvessel density, increased proliferating EC, dilated blood vessels, and notably less tumor cell apoptosis compared to noninduced controls. It was concluded that NRP1 expression results in enlarged tumors associated with substantially enhanced tumor angiogenesis.
Miao
H Q
HQ
Department of Surgical Research, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Lee
P
P
Lin
H
H
Soker
S
S
Klagsbrun
M
M
D000818:Animals; D002465:Cell Movement; D004317:Doxorubicin / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D039942:Neuropilin-1; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D017978:Receptors, Growth Factor / Q000096:biosynthesis; D040262:Receptors, Vascular Endothelial Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1; D004317:Doxorubicin; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor