PLoS ONE (Jan 2017)

E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness.

  • Marina Rosso,
  • Blanca Majem,
  • Laura Devis,
  • Lara Lapyckyj,
  • María José Besso,
  • Marta Llauradó,
  • María Florencia Abascal,
  • María Laura Matos,
  • Lucia Lanau,
  • Josep Castellví,
  • José Luis Sánchez,
  • Asunción Pérez Benavente,
  • Antonio Gil-Moreno,
  • Jaume Reventós,
  • Anna Santamaria Margalef,
  • Marina Rigau,
  • Mónica Hebe Vazquez-Levin

DOI
https://doi.org/10.1371/journal.pone.0184439
Journal volume & issue
Vol. 12, no. 9
p. e0184439

Abstract

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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.