RESUMO
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.
Assuntos
Caderinas/metabolismo , Neoplasias Ovarianas/metabolismo , Antígenos CD , Ascite/metabolismo , Ascite/patologia , Biomarcadores Tumorais/metabolismo , Antígeno Ca-125/sangue , Adesão Celular/fisiologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana/sangue , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , RNA Mensageiro/metabolismoRESUMO
OBJETIVOS: Analizar el efecto de extractos de Pygeum africanum sobre la proliferación de células de próstata humana, in vitro. MÉTODOS: Líneas celulares tumorales prostáticas, así como células epiteliales derivadas de hiperplasia benigna de próstata fueron puestas en cultivo y tratadas con extractos de P. africanum. El efecto sobre la proliferación celular fue monitorizado mediante incorporación de (3H)-timidina o bromodesoxiuridina y ensayos de citometría de flujo. RESULTADOS: La incubación con extractos de P. africanum, con o sin adición de aminoácidos, inhibe significativamente y de forma dosis-dependiente la proliferación de las líneas celulares derivadas de cáncer de próstata LNCaP, PZ-HPV-7, y CA-HPV-10. En las células PZ-HPV-7, los extractos de P. africanum contrarrestan la acción mitogénica de EGF y bloquean la transición G1 a S del ciclo celular. Los extractos de P. africanum ejercen también una potente acción antimitogénica sobre células epiteliales que derivan de explantes de hiperplasia benigna de próstata. CONCLUSIONES: Los extractos etanólicos de P. africanum tienen un efecto antimitogénico sobre células tumorales prostáticas y sobre células epiteliales derivadas de hiperplasia benigna de próstata. Dicho efecto está asociado a la inhibición de la acción mitogénica de EGF y se acompaña de una disminución de la entrada de las células en la fase S del ciclo celular (AU)
