E-Cadherin fragments as potential mediators for peritoneal metastasis in advanced epithelial ovarian cancer
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E-Cadherin fragments as potential mediators for peritoneal metastasis in advanced epithelial ovarian cancer. / Trillsch, Fabian; Kuerti, Sascha ; zu Eulenburg, Christine; Burandt, Eike; Woelber, Linn; Prieske, Katharina; Eylmann, Kathrin; Oliveira-Ferrer, Leticia; Milde-Langosch, Karin; Mahner, Sven.
in: BRIT J CANCER, Jahrgang 114, Nr. 2, 12.01.2016, S. 213-220.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - E-Cadherin fragments as potential mediators for peritoneal metastasis in advanced epithelial ovarian cancer
AU - Trillsch, Fabian
AU - Kuerti, Sascha
AU - zu Eulenburg, Christine
AU - Burandt, Eike
AU - Woelber, Linn
AU - Prieske, Katharina
AU - Eylmann, Kathrin
AU - Oliveira-Ferrer, Leticia
AU - Milde-Langosch, Karin
AU - Mahner, Sven
PY - 2016/1/12
Y1 - 2016/1/12
N2 - BACKGROUND: Peritoneal dissemination and retroperitoneal lymph node involvement are main routes for tumour spread of epithelial ovarian cancer (EOC), possibly determined by the intercellular connecting protein E-Cadherin (E-Cad) and its fragments.METHODS: Tumour tissue of 105 advanced EOC patients was evaluated for protein expression of E-Cad, β-Catenin and Calpain by western blotting and immunohistochemistry. Expression patterns were compared between tumours with solely intraperitoneal (pT3c, pN0; n=41) and tumours with retroperitoneal metastases (pT1a-3c, pN1; n=64). Lysates of the EOC cell line SKOV3 and tumour tissue from the intraperitoneal group were tested for E-Cad expression following Calpain treatment.RESULTS: E-Cad full-length (E-Cad-FL, 120 kDa) and two major fragments at 85 kDa (E-Cad-85) and 23 kDa (E-Cad-23) were detected by western blotting. E-Cad-85 expression was significantly higher in tumours with solely intraperitoneal metastases and correlated strongly with E-Cad-23 and the protease Calpain. Calpain-mediated cleavage was identified as a potential mechanism to generate E-Cad-85 from E-Cad-FL by treating lysates from SKOV3 cells and tumour tissue with this enzyme. Increased cytoplasmic localisation of β-Catenin in tumours with high E-Cad-85 expression corroborates that E-Cad-85 loses the binding site for β-Catenin after fragmentation, enabling tumour cluster formation and peritoneal dissemination.CONCLUSIONS: Calpain-mediated E-Cad fragmentation appears to promote intraperitoneal EOC progression. Understanding these mechanisms might eventually lead to new tailored subtype-specific diagnostic and therapeutic interventions.British Journal of Cancer advance online publication 12 January 2016. doi:10.1038/bjc.2015.436 www.bjcancer.com.
AB - BACKGROUND: Peritoneal dissemination and retroperitoneal lymph node involvement are main routes for tumour spread of epithelial ovarian cancer (EOC), possibly determined by the intercellular connecting protein E-Cadherin (E-Cad) and its fragments.METHODS: Tumour tissue of 105 advanced EOC patients was evaluated for protein expression of E-Cad, β-Catenin and Calpain by western blotting and immunohistochemistry. Expression patterns were compared between tumours with solely intraperitoneal (pT3c, pN0; n=41) and tumours with retroperitoneal metastases (pT1a-3c, pN1; n=64). Lysates of the EOC cell line SKOV3 and tumour tissue from the intraperitoneal group were tested for E-Cad expression following Calpain treatment.RESULTS: E-Cad full-length (E-Cad-FL, 120 kDa) and two major fragments at 85 kDa (E-Cad-85) and 23 kDa (E-Cad-23) were detected by western blotting. E-Cad-85 expression was significantly higher in tumours with solely intraperitoneal metastases and correlated strongly with E-Cad-23 and the protease Calpain. Calpain-mediated cleavage was identified as a potential mechanism to generate E-Cad-85 from E-Cad-FL by treating lysates from SKOV3 cells and tumour tissue with this enzyme. Increased cytoplasmic localisation of β-Catenin in tumours with high E-Cad-85 expression corroborates that E-Cad-85 loses the binding site for β-Catenin after fragmentation, enabling tumour cluster formation and peritoneal dissemination.CONCLUSIONS: Calpain-mediated E-Cad fragmentation appears to promote intraperitoneal EOC progression. Understanding these mechanisms might eventually lead to new tailored subtype-specific diagnostic and therapeutic interventions.British Journal of Cancer advance online publication 12 January 2016. doi:10.1038/bjc.2015.436 www.bjcancer.com.
U2 - 10.1038/bjc.2015.436
DO - 10.1038/bjc.2015.436
M3 - SCORING: Journal article
C2 - 26757261
VL - 114
SP - 213
EP - 220
JO - BRIT J CANCER
JF - BRIT J CANCER
SN - 0007-0920
IS - 2
ER -