J Cancer 2020; 11(24):7291-7301. doi:10.7150/jca.46429

Research Paper

VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma

Li Chen1,2*, Guoxiang Lin1*, Kaihua Chen2, Renba Liang2, Fangzhu Wan2, Chuxiao Zhang2, Ge Tian2, Xiaodong Zhu1,2,3✉

1. Department of Oncology, Affiliated Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530010, People's Republic of China.
2. Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi 530021, People's Republic of China.
3. Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi 530021, People's Republic of China.
*These authors contributed equally to this work.

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Chen L, Lin G, Chen K, Liang R, Wan F, Zhang C, Tian G, Zhu X. VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma. J Cancer 2020; 11(24):7291-7301. doi:10.7150/jca.46429. Available from https://www.jcancer.org/v11p7291.htm

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Background: Vascular endothelial growth factor (VEGF) is an important pro-angiogenic factor. Accumulating data have indicated that VEGF is involved in tumour metastasis. However, the mechanism through which VEGF regulates nasopharyngeal carcinoma (NPC) metastasis is largely unknown. This study aimed to examine the biological function of VEGF in NPC metastasis and its underlying mechanism.

Methods: We used western blotting and qPCR to examine the difference in VEGF expression between NPC cells and the immortalized nasopharyngeal epithelial cell line NP69. Wound healing assays, transwell assays and animal experiments were used to further verify the role of VEGF in the invasion and migration of NPC cells. The protein levels of the epithelial-mesenchymal transition (EMT) and matrix metalloproteinase (MMP) family were analysed by immunofluorescence (IF) and western blotting. Enzyme-linked immunosorbent assay (ELISA) and transwell assays were used to determine whether VEGF enhanced the invasion and migration of NPC cells in an autocrine manner. Western blotting was used to examine how autocrine VEGF-VEGFR2 signalling regulated EMT and MMPs.

Results: We observed higher levels of VEGF in NPC cells than that in NP69 cells and identified an association between high VEGF levels and tumour invasion and migration. Mechanistically, the VEGF-mediated increase in EMT markers, MMP2 and MMP9 promoted NPC cell invasion and migration. Additionally, NPC cells secreted VEGF to promote cell invasion, migration and angiogenesis. Autocrine VEGF-VEGFR2 signalling increased ERK1/2 phosphorylation, promoted EMT process and MMPs at the indicated times.

Conclusion: This study revealed that VEGF plays a role in controlling NPC cell metastasis by regulating EMT markers and MMPs in an autocrine manner.

Keywords: nasopharyngeal carcinoma, VEGF, invasion, migration