TY  - JOUR
A1  - Bekes, Inga
A1  - Löb, Sanja
A1  - Holzheu, Iris
A1  - Janni, Wolfgang
A1  - Baumann, Lisa
A1  - Wöckel, Achim
A1  - Wulff, Christine
T1  - Nectin‐2 in ovarian cancer: how is it expressed and what might be its functional role?
JF  - Cancer Science
N2  - 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.
KW  - metastasis
KW  - ovarian cancer
KW  - survival
KW  - Nectin‐2
KW  - VEGF
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202748
VL  - 110
IS  - 6
ER  -