Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression

Clin Exp Metastasis. 2008;25(6):643-55. doi: 10.1007/s10585-008-9171-5. Epub 2008 Apr 9.

Abstract

The mesodermally derived normal ovarian surface epithelium (OSE) displays both epithelial and mesenchymal characteristics and exhibits remarkable phenotypic plasticity during post-ovulatory repair. The majority of epithelial ovarian carcinomas (EOC) are derived from the OSE and represent the most lethal of all gynecological malignancies, as most patients (approximately 70%) present at diagnosis with disseminated intra-abdominal metastasis. The predominant pattern of EOC metastasis involves pelvic dissemination rather than lymphatic or hematologic spread, distinguishing EOC from other solid tumors. Acquisition of the metastatic phenotype involves a complex series of interrelated cellular events leading to dissociation (shedding) and dispersal of malignant cells. A key event in this process is disruption of cell-cell contacts via modulation of intercellular junctional components. In contrast to most carcinomas that downregulate E-cadherin expression during tumor progression, a unique feature of primary well-differentiated ovarian cancers is a gain of epithelial features, characterized by an increase in expression of E-cadherin. Subsequent reacquisition of mesenchymal features is observed in more advanced tumors with concomitant loss of E-cadherin expression and/or function during progression to metastasis. The functional consequences of this remarkable phenotypic plasticity are not fully understood, but may play a role in modulation of cell survival in suspension (ascites), chemoresistance, and intraperitoneal anchoring of metastatic lesions.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cadherins / metabolism*
  • Disease Progression
  • Epithelium / pathology*
  • Female
  • Humans
  • Mesoderm / pathology*
  • Neoplasm Invasiveness / pathology*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Phenotype

Substances

  • Cadherins