title: Neuropilin-2 expression in papillary thyroid carcinoma: correlation with VEGF-D expression, lymph node metastasis, and VEGF-D-induced aggressive cancer cell phenotype.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Laboratory Medicine, Wakayama Medical University, 811-1, Kimiidera, 641-8509 Wakayama City, Japan.
authors: Hironao
authors: H
authors: Yasuoka
authors: Rieko
authors: R
authors: Kodama
authors: Mitsuyoshi
authors: M
authors: Hirokawa
authors: Yuuki
authors: Y
authors: Takamura
authors: Akira
authors: A
authors: Miyauchi
authors: Michiya
authors: M
authors: Inagaki
authors: Tokio
authors: T
authors: Sanke
authors: Yasushi
authors: Y
authors: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D039943:Neuropilin-2 / Q000378:metabolism*; D010641:Phenotype; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D042643:Vascular Endothelial Growth Factor D / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D039943:Neuropilin-2; D042643:Vascular Endothelial Growth Factor D