Potential role for vascular endothelial growth factor‐D as an autocrine factor for human gastric carcinoma cells |
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| Authors: | Miwako Tanaka Yasuhiko Kitadai Michiyo Kodama Kei Shinagawa Tomonori Sumida Shinji Tanaka Naohide Oue Wataru Yasui Kazuaki Chayama |
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| Affiliation: | 1. Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima;2. Department of Endoscopy, Hiroshima University Hospital, Hiroshima;3. Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan |
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| 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 human gastric carcinoma by acting via autocrine and paracrine mechanisms. (Cancer Sci 2010) |
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