@article{BekesLoebHolzheuetal.2019,
  author    = {Bekes, Inga and L{\"o}b, Sanja and Holzheu, Iris and Janni, Wolfgang and Baumann, Lisa and W{\"o}ckel, Achim and Wulff, Christine},
  title     = {Nectin-2 in ovarian cancer: how is it expressed and what might be its functional role?},
  series = {Cancer Science},
  volume    = {110},
  journal   = {Cancer Science},
  number    = {6},
  doi       = {10.1111/cas.13992},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202748},
  pages     = {1872- 1882},
  year      = {2019},
  abstract  = {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.},
  language  = {en}
}