Serous borderline ovarian tumors in long-term culture: phenotypic and genotypic distinction from invasive ovarian carcinomas

Int J Gynecol Cancer. 2008 Nov-Dec;18(6):1234-47. doi: 10.1111/j.1525-1438.2007.01171.x. Epub 2008 Jan 23.

Abstract

Serous borderline ovarian tumors (SBOTs) are differentiated, slow growing, noninvasive, and have a better prognosis than their invasive counterparts, but recurrence and progression to invasive carcinomas are common, and unlike high-grade serous carcinomas, they tend to be nonresponsive to chemotherapy. However, due to a lack of culture systems and animal models, information about the properties of SBOT and their changes with neoplastic progression is extremely limited. Our objective was to establish a cell culture model for SBOTs and to characterize their phenotype and genotype. We compared cultures derived from two SBOTs, one of which was a short-term culture containing a BRAF mutation but few other cytogenetic changes while the other culture developed into a spontaneously immortalized permanent cell line and had numerical and structural chromosomal abnormalities but lacked RAS/BRAF mutations. Both cultures formed whorl-like epithelial colonies and resembled low-grade invasive carcinomas by their secretion of CA125 and oviduct-specific glycoprotein, production of matrix metalloproteinases, E-cadherin expression, and telomerase activity. Other characteristics associated with neoplastic transformation, including invasiveness, anchorage-independent growth, and tumorigenicity, were not observed. Importantly, cell motility was reduced in both lines, likely contributing to the lack of invasiveness. The results reveal a striking phenotypic similarity between the two cell lines, regardless of their cytogenetic diversity, which suggests that their characteristic phenotype is regulated to a large degree by epigenetic and environmental factors. In conclusion, we have established the first permanent SBOT cell line, which provides a new model to elucidate the undefined relationship of SBOTs to invasive ovarian carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Base Sequence
  • Biomarkers
  • Cell Differentiation
  • Cell Movement
  • Female
  • Gene Dosage / genetics
  • Genotype
  • Health
  • Humans
  • Mice
  • Mutation / genetics
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology*
  • Phenotype
  • Time Factors
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers