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Neuropilin-2 expression in papillary thyroid carcinoma: correlation with VEGF-D expression, lymph node metastasis,
Hironao Yasuoka1, Rieko Kodama, Mitsuyoshi Hirokawa
1Department of Clinical Laboratory Medicine, Wakayama Medical University, 811-1, Kimiidera, 641-8509 Wakayama City, Japan.
Context:
Neuropilin-2 (Nrp2) is a coreceptor for vascular endothelial growth factor-D (VEGF-D) that is expressed on the surface of endothelial cells. Recently, Nrp2 was shown to play a role in lymph node metastasis and promotion of cancer cell migration. VEGF-D also promotes lymphangiogenesis, which in turn promotes tumor metastasis.
Objective:
The aim was to study the role of neuropilin-2 in lymph node metastasis in human papillary thyroid carcinoma (PTC).
Design:
Expression of Nrp2 was studied by immunohistochemistry and the relationship between Nrp2 expression and lymph node metastasis, VEGF-D expression and other established clinicopathological variables were analyzed in PTC. The effects of neutralizing anti-Nrp2 antibody on VEGF-D-induced invasion and migration were assessed in PTC cell lines.
Results:
Nrp2 expression was observed in 64.3% (36 of 56) of the PTC patients. Nrp2 expression was significantly correlated with lymph node metastasis (P = 0.0216) and VEGF-D expression (P = 0.0034). VEGF-D was shown to promote filopodia formation and cancer cell migration and invasion by K1 and B-CPAP cells. These responses were significantly blocked by neutralizing anti-Nrp2 antibody.
Conclusion:
Nrp2 expression was correlated with lymph node metastasis and VEGF-D expression in PTC. Our data also showed a role for Nrp2 in regulating VEGF-D-induced invasion and migration in vitro.