Promotion of metastasis of thyroid cancer cells via NRP-2-mediated induction

• Published in: Oncology letters Vol. 12; no. 5; pp. 4224 - 4230
• Main Authors: Tu, Dom-Gene, Chang, Wen-Wei, Jan, Ming-Shiou, Tu, Chi-Wen, Lu, Yin-Che, Tai, Chien-Kuo
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.11.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Binding sites; Care and treatment; Cell adhesion & migration; Complications and side effects; Gene expression; Genetic aspects; Health aspects; Kinases; lymphangiogenesis; Lymphatic system; Membrane proteins; Metastasis; NRP-2; Oncology; Penicillin; Signal transduction; Studies; Thyroid cancer; tumor metastasis; Tumors; Vascular endothelial growth factor; VEGF-C; United States > US; NRP-2; lymphangiogenesis; VEGF-C; thyroid cancer; tumor metastasis
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2016.5153

Tumor-node-metastasis is one of the leading causes of morbidity and mortality in thyroid cancer patients. Upregulation of vascular endothelial growth factor-C (VEGF-C) increases the migratory ability of thyroid cancer cells to lymph nodes. Expression of neuropilin-2 (NRP-2), the co-receptor of VEGF-C, has been reported to be correlated with lymph node metastasis in human thyroid cancer. The present study investigated the role of VEGF-C/NRP-2 signaling in the regulation of metastasis of two different types of human thyroid cancer cells. The results indicated that the VEGF-C/NRP-2 axis significantly promoted the metastatic activities of papillary thyroid carcinoma cells through the activation of the mitogen-activated protein kinase (MAPK) kinase (MEK)/extracellular signal-regulated kinase and p38 MAPK signaling cascades. However, neither MEK or p38 MAPK inhibitors produced significant inhibition of the migratory activity and invasiveness regulated by the VEGF-C/NRP-2 axis in follicular thyroid carcinoma cells. Finally, VEGF-C/NRP-2-mediated invasion and migration of thyroid cancer cells required the expression of NRP-2. The present results demonstrate that the promotion of metastasis by VEGF-C is mainly due to the upregulation of NRP-2 in thyroid cancer cells, and this metastatic activity regulated by the VEGF-C/NRP-2 axis provides further insight into the process of tumor metastasis.