Background: Epithelial ovarian carcinoma is one of the most aggressive among gynaecological tumours and is often diagnosed at advanced stages with very poor prognosis. Despite advances in surgical and chemotherapeutic strategies, only marginal improvement in patient outcome has been obtained. Hence, understanding the biological mechanisms underlying ovarian cancer progression is critical for its treatment. We reported that CD157 (BST-1), an ectoenzyme regulating leukocyte diapedesis during inflammation, is expressed by 90% of epithelial ovarian cancers and high CD157 expression is associated with poor outcome in patients. Material and methods: We assessed the relevance of CD157 in tumour migration and dissemination by transfecting CD157 cDNA in CD157-negative NIH:OVCAR-3 cells and in OV-90 cells expressing low CD157, or by knocking down CD157 expression in OV-90 cells. These cells were used as in vitro models to dissect the functional role of CD157 during crucial steps of ovarian cancer progression. Results: Exogenous expression of CD157 in NIH:OVCAR-3 and overexpression in OV-90 cells demonstrated that high levels of CD157 induce morphological and functional modifications reminiscent of mesenchymal-like differentiation and promote tumour cell survival by inhibiting anoikis. The effects of CD157 overexpression on ovarian cancer cells phenotype translate into increased tumour cell motility, mesothelial invasion and matrix metalloproteinases activity. Conversely, knockdown of CD157 in OV-90 cells reverts the mesenchymal phenotype and reduces the migratory potential, implying a direct correlation between CD157 expression levels and tumour aggressiveness. Gene profile analysis highlighted 378 significantly deregulated genes representing the signature of CD157-overexpressing ovarian cancer cells. The analysis of these transcripts indicated that expression of CD157 strengthens a number of pro-metastatic biological processes (such as motility and invasiveness), and represses several biological processes counteracting tumour progression (such as apoptosis, cell death and response to stress). Conclusions: Collectively, these findings support a role of CD157 in the control of ovarian cancer progression and motivate the existence of a direct correlation between the expression levels of CD157 and the adverse clinical outcome in patients.
Involvement of CD157 in the control of ovarian cancer progression
LO BUONO, NICOLA;MORONE, SIMONA;PARROTTA, ROSSELLA;GIACOMINO, ALICE;FERRERO, Enza;VOLANTE, Marco;FUNARO, Ada;ORTOLAN, Erika
2012-01-01
Abstract
Background: Epithelial ovarian carcinoma is one of the most aggressive among gynaecological tumours and is often diagnosed at advanced stages with very poor prognosis. Despite advances in surgical and chemotherapeutic strategies, only marginal improvement in patient outcome has been obtained. Hence, understanding the biological mechanisms underlying ovarian cancer progression is critical for its treatment. We reported that CD157 (BST-1), an ectoenzyme regulating leukocyte diapedesis during inflammation, is expressed by 90% of epithelial ovarian cancers and high CD157 expression is associated with poor outcome in patients. Material and methods: We assessed the relevance of CD157 in tumour migration and dissemination by transfecting CD157 cDNA in CD157-negative NIH:OVCAR-3 cells and in OV-90 cells expressing low CD157, or by knocking down CD157 expression in OV-90 cells. These cells were used as in vitro models to dissect the functional role of CD157 during crucial steps of ovarian cancer progression. Results: Exogenous expression of CD157 in NIH:OVCAR-3 and overexpression in OV-90 cells demonstrated that high levels of CD157 induce morphological and functional modifications reminiscent of mesenchymal-like differentiation and promote tumour cell survival by inhibiting anoikis. The effects of CD157 overexpression on ovarian cancer cells phenotype translate into increased tumour cell motility, mesothelial invasion and matrix metalloproteinases activity. Conversely, knockdown of CD157 in OV-90 cells reverts the mesenchymal phenotype and reduces the migratory potential, implying a direct correlation between CD157 expression levels and tumour aggressiveness. Gene profile analysis highlighted 378 significantly deregulated genes representing the signature of CD157-overexpressing ovarian cancer cells. The analysis of these transcripts indicated that expression of CD157 strengthens a number of pro-metastatic biological processes (such as motility and invasiveness), and represses several biological processes counteracting tumour progression (such as apoptosis, cell death and response to stress). Conclusions: Collectively, these findings support a role of CD157 in the control of ovarian cancer progression and motivate the existence of a direct correlation between the expression levels of CD157 and the adverse clinical outcome in patients.
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