American Journal of Cancer Research | |
VEGF-C-VEGFR3/Flt4 axis regulates mammary tumor growth and metastasis in an autocrine manner | |
Michelle L Varney1  Rakesh K Singh1  | |
关键词: Breast cancer; vascular endothelial growth factor-C; vascular endothelial growth factor receptor-3; lymphangiogenesis; metastasis; | |
DOI : | |
学科分类:肿瘤学 | |
来源: e-Century Publishing Corporation | |
【 摘 要 】
Purpose: Lymphangiogenic factors, such as vascular endothelial growth factor-C (VEGF-C) and VEGFC-D, and their receptor, VEGF receptor-3 (VEGFR3), play a pivotal role in the promotion of metastasis to regional lymph nodes. In the present study we explored the role of VEGF-C as an autocrine growth factor for breast cancer cells. Methods: We examined the expression of VEGF-C and VEGFR3 in mammary tumor cells lines and examined whether blocking the VEGF-C-VEGFR3/Flt4 pathway using a VEGFR3 antagonist would inhibit proliferation of mammary tumor cells resulting in a decrease in tumor growth and metastasis. Results: We report expression of VEGF-C and its receptor VEGFR3 by mammary tumor cells, and their association with aggressiveness. Inhibition of VEGF-C-VEGFR3/Flt4 in mammary tumor cells decreased their proliferation and survival. Mammary tumor bearing mice treated with a VEGFR3 antagonist showed a significant decrease in tumor growth and the extent of spontaneous and experimental lung metastases. Conclusion: These findings demonstrate the VEGF-C-VEGFR3/Flt4 autocrine signaling pathway regulates mammary tumor cell survival and proliferation and that neutralization of VEGFR3 signaling might lead to development of a novel therapeutic approach for malignant breast cancer.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
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RO201912140867545ZK.pdf | 4680KB | download |