A potential role for vascular endothelial growth factor-D as an autocrine growth factor for human breast carcinoma cells.
BACKGROUND
Vascular endothelial growth factor-D (VEGF-D) binds and activates vascular endothelial growth factor receptor-2 (VEGFR-2), which signals for angiogenesis, and VEGFR-3, which signals for lymphangiogenesis. Besides endothelial cells, VEGFR-2 has been detected on malignant cells, including human breast carcinoma cells.


METHODS
It was examined if ectopic expression of human VEGF-D affected growth of breast carcinoma cell lines in vitro and in vivo.


RESULTS
VEGF-D overexpressing clonal MCF-7 and MDA-MB-231 cell lines displayed increased proliferative activities and upregulation of cyclins A, D1 and D3, compared to the vector control. Following subcutaneous inoculation of the MDA-MB-231 cells into nude mice, growth of the VEGF-D overexpressing cells was greatly accelerated. The tumor weight gain was accompanied by increased proliferative activity, cyclin A expression and microvascular density.


CONCLUSIONS
These findings suggest that VEGF-D functions both as an autocrine growth factor and a stimulator of angiogenesis in breast cancer.
Akahane
Manabu
M
Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892-4255, USA.
Akahane
Takemi
T
Shah
Amy
A
Okajima
Eijiro
E
Thorgeirsson
Unnur P
UP
D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation; D042643:Vascular Endothelial Growth Factor D / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
C534696:CCND3 protein, human; C534697:Ccnd3 protein, mouse; D019925:Cyclin A; D056743:Cyclin D3; D016213:Cyclins; D018076:DNA, Complementary; D042643:Vascular Endothelial Growth Factor D; D019938:Cyclin D1