| Summary: | 博士 === 國立中正大學 === 分子生物研究所 === 102 === Thyroid cancer is the most common malignant tumor of the endocrine system. The mainstay of treatment of thyroid carcinoma is surgery. Well-differentiated papillary and follicular carcinomas can be effectively treated by surgery followed by radioiodine therapy. However, poorly-differentiated tumors or unresectable follicular cell-derived tumors together with C cell-derived medullary carcinomas usually fail with traditional treatment and have an unfavorable prognosis. Meanwhile, 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 migration ability of thyroid cancer cells to lymph nodes. Expression of neuropilin-2 (NRP-2), the coreceptor of VEGF-C, has been reported to be correlated with lymph node metastasis in human thyroid cancer. In this paper, we present our investigation of VEGF-C/NRP-2 signaling in the regulation of metastasis of different types of human thyroid cancer cells. In our study, the VEGF-C/NRP-2 axis significantly promoted the metastatic activities of papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) cells through the activation of the MEK/ERK and p38 MAPK signaling cascades. However, both the MEK and p38 MAPK inhibitors showed no significant inhibition on the migratory activity and invasiveness regulated by the VEGF-C/NRP-2 axis in follicular thyroid carcinoma (FTC) cells. Finally, we found that VEGF-C/NRP-2-mediated invasion and migration of all three thyroid cancer cells required expression of NRP-2. Our results demonstrate that the promotion of metastasis by VEGF-C is mainly due to the upregulation of NRP-2 on thyroid cancer cells. The metastatic activity regulated by the VEGF-C/NRP-2 axis provides further insight into the process of tumor metastasis, and the VEGF-C or NRP2-based therapeutic strategy can offer an alternative treatment for thyroid cancer.
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