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

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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 (∼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.

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Acknowledgments

This work was supported by National Cancer Institute Research Grants RO1CA090492 (LGH), CA109545 (MSS), and CA86984 (MSS). The authors wish to gratefully acknowledge the Robert H. Lurie Comprehensive Cancer Center Pathology Core Facility for ovarian tumor tissues and Dr. Brian P. Adley (Lutheran General Hospital, IL) for scoring of the immunohistochemical analyses.

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  1. Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA

    Laurie G. Hudson & Reema Zeineldin

  2. Department of Pathology and Anatomical Sciences, School of Medicine, University of Missouri, 1 Hospital Drive, M214E Medical Sciences Building, Columbia, MO, 65212, USA

    M. Sharon Stack

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  1. Laurie G. Hudson
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Correspondence to M. Sharon Stack.

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Hudson, L.G., Zeineldin, R. & Stack, M.S. Phenotypic plasticity of neoplastic ovarian epithelium: unique cadherin profiles in tumor progression. Clin Exp Metastasis 25, 643–655 (2008). https://doi.org/10.1007/s10585-008-9171-5

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