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

Tu,Dom‑Gene; Chang,Wen‑Wei; Jan,Ming‑Shiou; Tu,Chi‑Wen; Lu,Yin‑Che; Tai,Chien‑Kuo

doi:10.3892/ol.2016.5153

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

Authors:
- Dom‑Gene Tu
- Wen‑Wei Chang
- Ming‑Shiou Jan
- Chi‑Wen Tu
- Yin‑Che Lu
- Chien‑Kuo Tai
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Affiliations: Department of Nuclear Medicine, Ditmanson Medical Foundation, Chia‑Yi Christian Hospital, Chia‑Yi 600, Taiwan, R.O.C., School of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C., Immunology Research Center, Chung Shan Medical University, Taichung 402, Taiwan, R.O.C., Department of Surgery, Ditmanson Medical Foundation, Chia‑Yi Christian Hospital, Chia‑Yi 600, Taiwan, R.O.C., Department of Hematology‑Oncology, Ditmanson Medical Foundation, Chia‑Yi Christian Hospital, Chia‑Yi 600, Taiwan, R.O.C., Department of Life Science, Institutes of Molecular Biology and Biomedical Science, National Chung Cheng University, Min‑Hsiung, Chia‑Yi 621, Taiwan, R.O.C.
Published online on: September 20, 2016 https://doi.org/10.3892/ol.2016.5153
Pages: 4224-4230

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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.

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