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

Trillsch, Fabian; Kuerti, Sascha; Eulenburg, Christine; Burandt, Eike; Woelber, Linn; Prieske, Katharina; Eylmann, Kathrin; Oliveira‐Ferrer, Leticia; Milde‐Langosch, Karin; Mahner, Sven

doi:10.1038/bjc.2015.436

Cited by 39 publications

(28 citation statements)

References 23 publications

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“…Recent studies have shown that the tumor cell differentiation status (epithelial-mesenchymal transition) might influence the route of metastasis in ovarian cancer [ 38 ]. Accordingly, we could demonstrate that a 85 kDa fragment of the epithelial marker E-Cadherin is associated with intraperitoneal metastasis, whereas VEGF-C and VEGF-D are more highly expressed in tumors displaying retroperitoneal tumor spread [ 39 , 40 ]. Although CEACAM1 expression does not correlate with the mode of OvCa metastasis, its relevance for patient outcome strongly differs between both ovarian cancer types.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

et al. 2018

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The underlying mechanisms of ovarian cancer (OvCa) dissemination are still poorly understood, and novel molecular markers for this cancer type are urgently needed. In search of adhesion molecules with prognostic relevance in OvCa, we compared tumors with good outcome (alive > 3 years) and those with poor outcome (dead < 2 years) within data from The Cancer Genome Atlas (TCGA). The carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) turned out as the only gene with differential expression in these groups. In order to further investigation on its role in OvCa, we analyzed CEACAM1 mRNA levels extracted from TCGA microarray data (n = 517) as well as CEACAM1 protein expression by Western blot analysis in a cohort of 242 tumor samples. Further, CEACAM1 localization in tumour tissue was evaluated by immunohistochemistry and CEACAM1 splice variants by RT-PCR in representative tumours. In Kaplan–Meier analysis, high CEACAM1 mRNA levels significantly correlated with longer survival (p = 0.008). By Western blot analysis in the second cohort, similar associations of high CEACAM1 protein levels with longer recurrence-free survival (RFS, p = 0.035) and overall survival (OAS, p = 0.004) were observed. In multivariate Cox regression analysis including clinical prognostic parameters, CEACAM1 mRNA or protein expression turned out as independent prognostic markers. Stratified survival analysis showed that high CEACAM1 protein expression was prognostic in node-negative tumors (p = 0.045 and p = 0.0002 for DFS and OAS) but lost prognostic significance in node-positive carcinomas. Similarly, high CEACAM1 mRNA expression did not show prognostic relevance in tumors with lymphatic invasion (L1) but was associated with longer survival in cases without lymphovascular involvement. Further analysis showed a predominance of 4S and 4L isoforms and mostly membraneous CEACAM1 localization in ovarian tumours. Our results suggest that CEACAM1 might be an independent favorable prognostic marker in OvCa, especially in the subgroup of patients with solely intraperitoneal metastasis.

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Section: Discussionmentioning

confidence: 99%

Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

et al. 2018

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“…Protein extraction from tumour samples and polyacrylamide gel electrophoresis were performed as described before. 15 Briefly, equal amounts of protein (20 μg) of each sample were loaded per well and equal loading was verified by immunoblotting with GAPDH antibody. As positive control, a protein extract from SKOV3 was loaded in each gel.…”

Section: Methodsmentioning

confidence: 99%

Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation

et al. 2019

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Background Maturation of complex N-glycans involves the action of Golgi mannosidases and plays a major role in cancer progression. We recently showed a favourable prognostic role of α-mannosidase MAN1A1 in breast cancer mainly caused by alteration of certain adhesion molecules. Methods We analysed the protein expression of MAN1A1 in ovarian cancer ( n = 204) using western blot and studied the impact of MAN1A1 itself and of MAN1A1-related glycosylation on the prognostic relevance of two adhesion molecules. Functional consequences of mannosidase inhibition using kifunensine and MAN1A1 knock out were investigated in ovarian cancer cells in vitro. Results Patients with high MAN1A1 expression in tumours showed significantly shorter RFS than those with low-MAN1A1 levels. Moreover, high MAN1A1 expression correlated significantly with advanced stage, lymph node involvement and distant metastasis. Further, the glycosylated adhesion molecule ALCAM reveals a significant adverse prognostic effect only in the presence of high MAN1A1 expression. In spheroid-formation assays, mannosidase inhibition and especially MAN1A1 knock out led to strong reduction of tumour cell aggregation. Conclusions Our study demonstrates the unfavourable prognostic role of MAN1A1 in ovarian cancer, probably caused by an altered ability of spheroid formation, and the strong influence of this glycosylation enzyme on the prognostic impact of ALCAM.

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“…Genetic variants of the E-cadherin gene were reported to be a prognostic marker to identify patients at increased risk of invasive or metastatic cancer (8). E-cadherin fragmentation was revealed to promote the progression of intraperitoneal epithelial ovarian cancer (9). However, the effects of CD44 and E-cadherin overexpression on cell proliferation, adhesion and invasion of ovarian cancer cells have remained elusive.…”

Section: Introductionmentioning

confidence: 99%

Effects of CD44 and E‑cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells

et al. 2017

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Abstract. CD44 is a prognostic indicator of shorter survival time in ovarian cancer. E-cadherin fragmentation promotes the progression of ovarian cancer. However, the effects of CD44 and E-cadherin overexpression on ovarian cancer cells have remained elusive. The present study aimed to investigate the effects of overexpression of CD44 and E-cadherin on cell proliferation, adhesion and invasion of SKOV-3 and OVCAR-3 ovarian cancer cells. Overexpression of CD44 and E-cadherin was achieved by transfecting SKOV-3 and OVCAR-3 cells with viruses carrying the CD44 or E-cadherin gene, respectively. Expression of CD44 and E-cadherin was detected by western blot analysis. The proliferation of SKOV-3 and OVCAR-3 cells was measured by a Cell Counting Kit-8 at 0, 24 and 48 h after viral transfection. The adhesion ability of SKOV-3 and OVCAR-3 cells to the endothelial layer was detected. A Transwell invasion assay was utilized to assess the invasion ability of the cells. Overexpression of CD44 and E-cadherin in SKOV-3 and OVCAR-3 cells was confirmed by western blot. Compared with the blank or negative control groups, the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells exhibited an increased cell proliferation rate at 24 and 48 h, whereas overexpression of E-cadherin did not alter the proliferation of these cells. Furthermore, compared with the blank and negative control groups, the cell adhesion and invasion ability in the CD44 overexpression groups of SKOV-3 and OVCAR-3 cells was markedly higher. There were no significant differences in adhesion ability between the E-cadherin overexpression group and the blank/negative control group. Of note, overexpression of E-cadherin decreased the invasive ability of SKOV-3 and OVCAR-3 cells. In conclusion, Overexpression of CD44 increased the proliferation, adhesion and invasion of ovarian cancer cells, while overexpression of E-cadherin decreased the invasion of ovarian cancer cells. IntroductionOvarian cancer is a common malignant tumor type of the female reproductive system with a high mortality rate. The 5-year survival rate of patients with ovarian cancer is 25-30% (1). Although progress has been made in the treatment of ovarian cancer, the mortality rate remains high. The majority of ovarian cancer patients have tumor metastasis at the time-point of diagnosis, and tumor invasion and metastasis are important causes of treatment failure (2). Therefore, investigation of the molecular mechanisms involved in tumor proliferation, adhesion and invasion is of great importance for improving the therapeutic effectiveness of ovarian cancer treatments.CD44 is a transmembrane protein that mediates cell-cell interactions as well as cell adhesion and migration. It is widely expressed on the cell surface (3). CD44 participates in numerous biological processes such as tumor metastasis, hematopoiesis, lymphocyte activation, recirculation and homing. CD44 is a receptor for hyaluronic acid and interacts with other ligands, such as matrix metalloproteinases, collagens and osteopontin (3). Posit...

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

Cited by 39 publications

References 23 publications

Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

Prognostic Impact of CEACAM1 in Node-Negative Ovarian Cancer Patients

Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation

Effects of CD44 and E‑cadherin overexpression on the proliferation, adhesion and invasion of ovarian cancer cells

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