Potential role for vascular endothelial growth factor-D as an autocrine factor for human gastric carcinoma cells

Cancer Science
Miwako TanakaKazuaki Chayama

Abstract

Vascular endothelial growth factor (VEGF)-D induces lymphangiogenesis by activating VEGF receptor (VEGFR)-3, which is expressed mainly by lymphatic endothelial cells. VEGFR-3 has also been detected in several types of malignant cells, but the significance of VEGFR-3 expression by malignant cells remains unclear. We examined the expression and function of VEGF-D/VEGFR-3 in human gastric carcinoma cells. Expression of VEGF-D and VEGFR-3 was analyzed in three human gastric carcinoma cell lines and 29 surgical specimens. cDNA microarray analysis was used to examine the effect of VEGF-D on the expression of genes associated with disease progression in VEGFR-3-expressing KKLS cells. VEGF-D-transfected cells and control cells were transplanted into the gastric wall of nude mice. In 10 of the 29 (34%) gastric carcinoma specimens and two of the three cell lines, cancer cells expressed both VEGF-D and VEGFR-3. In vitro treatment of KKLS cells with exogenous VEGF-D increased expression of cyclin D1 and Bcl-2 and stimulated cell proliferation. VEGF-D transfection into KKLS cells resulted in stimulation of angiogenesis, lymphangiogenesis, and cell proliferation, and in inhibition of apoptosis. VEGF-D may participate in the progression of hu...Continue Reading

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Citations

Apr 13, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Ryota EbataYoichi Kohno
Jan 20, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Jill M SiegfriedLaura P Stabile
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Jun 4, 2011·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Jung Yeon KimKyeongmee Park

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