title: Promotion of metastasis of thyroid cancer cells via NRP-2-mediated induction.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chia-Yi 600, Taiwan, R.O.C.; Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan, R.O.C.; College of Health Sciences, Chang Jung Christian University, Tainan 711, Taiwan, R.O.C.
authors.forename: Dom-Gene
authors.initials: DG
authors.lastname: Tu
authors.affiliation: School of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Chang
authors.affiliation: Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.; Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C.; Division of Allergy, Immunology and Rheumatology, Chia-Yi Christian Hospital, Chia-Yi 600, Taiwan, R.O.C.
authors.forename: Ming-Shiou
authors.initials: MS
authors.lastname: Jan
authors.affiliation: Department of Surgery, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chia-Yi 600, Taiwan, R.O.C.
authors.forename: Chi-Wen
authors.initials: CW
authors.lastname: Tu
authors.affiliation: Department of Hematology-Oncology, Ditmanson Medical Foundation, Chia-Yi Christian Hospital, Chia-Yi 600, Taiwan, R.O.C.
authors.forename: Yin-Che
authors.initials: YC
authors.lastname: Lu
authors.affiliation: Department of Life Science, Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan, R.O.C.
authors.forename: Chien-Kuo
authors.initials: CK
authors.lastname: Tai
keywords: NRP-2; VEGF-C; lymphangiogenesis; thyroid cancer; tumor metastasis