Nectin-2 in ovarian cancer: How is it expressed and what might be its functional role?

Cancer Sci. 2019 Jun;110(6):1872-1882. doi: 10.1111/cas.13992. Epub 2019 May 2.


Nectin-2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin-2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin-2 and CD31 using immunohistochemistry. Gene expression of Nectin-2 was quantified by real-time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin-2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin-2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin-2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin-2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin-2 which was reversed by VEGF-inhibition. In addition, Nectin-2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin-2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF-induced Nectin-2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production.

Keywords: Nectin-2; VEGF; metastasis; ovarian cancer; survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Capillary Permeability / drug effects
  • Capillary Permeability / genetics
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Nectins / genetics*
  • Nectins / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Peritoneum / metabolism
  • RNA Interference
  • Vascular Endothelial Growth Factors / blood
  • Vascular Endothelial Growth Factors / metabolism
  • Vascular Endothelial Growth Factors / pharmacology
  • Young Adult


  • NECTIN2 protein, human
  • Nectins
  • Vascular Endothelial Growth Factors