| Autor: |
Rosso M; Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Buenos Aires, Argentina., Majem B; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Devis L; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Lapyckyj L; Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Buenos Aires, Argentina., Besso MJ; Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Buenos Aires, Argentina., Llauradó M; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Abascal MF; Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Buenos Aires, Argentina., Matos ML; Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Buenos Aires, Argentina., Lanau L; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Castellví J; Pathology Department, Vall Hebron University Hospital, Barcelona, Spain., Sánchez JL; Gynecology Oncology Department, Vall Hebron University Hospital, Barcelona, Spain., Pérez Benavente A; Gynecology Oncology Department, Vall Hebron University Hospital, Barcelona, Spain., Gil-Moreno A; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain.; Gynecology Oncology Department, Vall Hebron University Hospital, Barcelona, Spain., Reventós J; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Santamaria Margalef A; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Rigau M; Biomedical Research Unit in Gynecology, Vall Hebron Research Institute and University Hospital, Barcelona, Spain., Vazquez-Levin MH; Laboratorio de Estudios de la Interacción Celular en Reproducción y Cáncer, Instituto de Biología y Medicina Experimental (IBYME; CONICET-FIBYME), Buenos Aires, Argentina. |
| Abstrakt: |
Ovarian cancer (OC) is the fifth cancer death cause in women worldwide. The malignant nature of this disease stems from its unique dissemination pattern. Epithelial-to-mesenchymal transition (EMT) has been reported in OC and downregulation of Epithelial cadherin (E-cadherin) is a hallmark of this process. However, findings on the relationship between E-cadherin levels and OC progression, dissemination and aggressiveness are controversial. In this study, the evaluation of E-cadherin expression in an OC tissue microarray revealed its prognostic value to discriminate between advanced- and early-stage tumors, as well as serous tumors from other histologies. Moreover, E-cadherin, Neural cadherin (N-cadherin), cytokeratins and vimentin expression was assessed in TOV-112, SKOV-3, OAW-42 and OV-90 OC cell lines grown in monolayers and under anchorage-independent conditions to mimic ovarian tumor cell dissemination, and results were associated with cell aggressiveness. According to these EMT-related markers, cell lines were classified as mesenchymal (M; TOV-112), intermediate mesenchymal (IM; SKOV-3), intermediate epithelial (IE; OAW-42) and epithelial (E; OV-90). M- and IM-cells depicted the highest migration capacity when grown in monolayers, and aggregates derived from M- and IM-cell lines showed lower cell death, higher adhesion to extracellular matrices and higher invasion capacity than E- and IE-aggregates. The analysis of E-cadherin, N-cadherin, cytokeratin 19 and vimentin mRNA levels in 20 advanced-stage high-grade serous human OC ascites showed an IM phenotype in all cases, characterized by higher proportions of N- to E-cadherin and vimentin to cytokeratin 19. In particular, higher E-cadherin mRNA levels were associated with cancer antigen 125 levels more than 500 U/mL and platinum-free intervals less than 6 months. Altogether, E-cadherin expression levels were found relevant for the assessment of OC progression and aggressiveness. |
