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Updated: Jun 27, 2026
Heterotypic Three-dimensional In Vitro Modeling of Stromal-Epithelial Interactions During Ovarian Cancer Initiation and Progression
Published on: August 28, 2012
Chromosomes 6 and 18 induce neoplastic suppression in epithelial ovarian cancer cells
Dimitra Dafou1, Susan J Ramus, Ken Choi
1Gynaecological Cancer Research Laboratory, UCL EGA Institute for Women's Health, University College London, London, United Kingdom. d.dafou@ucl.ac.uk
Abstract:
Metaphase comparative genomic hybridisation (CGH) studies indicate that chromosomes 4, 5, 6, 13, 14, 15 and 18 are frequently deleted in primary ovarian cancers (OCs). Therefore we used microcell-mediated chromosome transfer (MMCT) to establish the functional effects of transferring normal copies of these chromosomes into 2 epithelial OC cell lines (TOV112D and TOV21G). The in vitro neoplastic phenotype (measured as anchorage dependent and independent growth and invasion) was compared between recipient OC cell lines and multiple MMCT hybrids. Chromosomes 6 and 18 showed strong evidence of functional, neoplastic suppression for multiple hybrids in both cell lines. We also found evidence in 1 cancer cell line suggesting that chromosomes 4, 13 and 14 may also cause functional suppression. Array CGH and microsatellite analyses were used to characterise the extent of genomic transfer in chromosome 6 and 18 hybrids. A 36 MB deletion on chromosome 6 in 2 hybrids from 1 cell line mapped the candidate region proximal to 6q15 and distal to 6q22.2; and an approximately 10 MB candidate region spanning the centromere on chromosome 18 was identified in 2 hybrids from the other cell line. These data support reported functional effects of chromosome 6 in OC cell lines; but to our knowledge, this is the first time that functional suppression for chromosome 18 has been reported. This suggests that these chromosomes may harbour tumour suppressor-"like" genes. The future identification of these genes may have a significant impact on the understanding and treatment of the disease and the identification of novel therapeutic targets.
Insights
Restoring chromosomes 6 and 18 in ovarian cancer cells suppressed tumor growth, suggesting these chromosomes may contain tumor suppressor genes. This finding offers potential new targets for ovarian cancer treatment.
Area of Science:
- Oncology
- Genetics
- Cell Biology
Background:
- Comparative genomic hybridization (CGH) studies frequently identify deletions on chromosomes 4, 5, 6, 13, 14, 15, and 18 in primary ovarian cancers (OCs).
- Understanding the functional impact of these chromosomal losses is crucial for identifying ovarian cancer tumor suppressor genes.
Purpose of the Study:
- To investigate the functional effects of introducing normal chromosome copies into ovarian cancer cell lines.
- To identify chromosomes that exhibit tumor suppressor activity in epithelial ovarian cancer.
Main Methods:
- Microcell-mediated chromosome transfer (MMCT) was used to introduce normal chromosomes into two ovarian cancer cell lines (TOV112D and TOV21G).
- In vitro neoplastic phenotypes, including anchorage-dependent and independent growth and invasion, were assessed in recipient cell lines and MMCT hybrids.
- Array CGH and microsatellite analyses were performed to characterize genomic transfer in hybrids involving chromosomes 6 and 18.
Main Results:
- Chromosomes 6 and 18 demonstrated significant neoplastic suppression in multiple hybrids across both cell lines.
- Evidence suggested that chromosomes 4, 13, and 14 may also possess functional suppression capabilities in one cell line.
- A 36 MB region on chromosome 6 (proximal to 6q15, distal to 6q22.2) and a ~10 MB region on chromosome 18 (spanning the centromere) were identified as candidate suppressor regions.
Conclusions:
- Chromosome 18 exhibits functional tumor suppressor activity in ovarian cancer cells, a finding reported here for the first time.
- Chromosomes 6 and 18 likely harbor tumor suppressor genes that can inhibit ovarian cancer cell proliferation and invasion.
- Identification of these tumor suppressor genes could lead to novel therapeutic targets and improved understanding of ovarian cancer pathogenesis.
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