E-Cadherin fragments as potential mediators for peritoneal metastasis in advanced epithelial ovarian cancer.

Abstract

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.

• Authors: Fabian Trillsch, Sascha Kuerti, Christine Eulenburg, Eike Burandt, Linn Woelber, Katharina Prieske, Kathrin Eylmann, Leticia Oliveira-Ferrer, Karin Milde-Langosch, Sven Mahner
• Journal: British journal of cancer (Br J Cancer) Vol. 114 Issue 2 Pg. 213-20 (Jan 19 2016) ISSN: 1532-1827 [Electronic] England
• PMID: 26757261 (Publication Type: Journal Article)

Chemical References

• Cadherins
• Peptide Fragments
• beta Catenin
• Calpain

Topics

• Adult
• Aged
• Aged, 80 and over
• Blotting, Western
• Cadherins (metabolism)
• Calpain (metabolism)
• Carcinoma, Ovarian Epithelial
• Cell Line, Tumor
• Female
• Humans
• Immunohistochemistry
• Lymph Nodes (metabolism, pathology)
• Middle Aged
• Neoplasms, Glandular and Epithelial (metabolism, pathology)
• Ovarian Neoplasms (metabolism, pathology)
• Peptide Fragments (metabolism)
• Peritoneal Neoplasms (metabolism, secondary)
• Retroperitoneal Neoplasms (metabolism, secondary)
• Retroperitoneal Space
• Retrospective Studies
• beta Catenin (metabolism)