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  • Review Article
  • Published:

Ovarian Cancer Metastasis: Integrating insights from disparate model organisms

Key Points

  • The lethality of ovarian carcinoma primarily stems from the inability to detect the disease at an early, organ-confined stage, and the lack of effective therapies for advanced-stage disease. So there is a need for new therapeutic targets and a better understanding of the mechanisms involved in the spread of ovarian carcinoma.

  • A widely recognized behaviour of ovarian carcinoma is its ability to seed the peritoneal cavity with nests of tumour cells and the formation of ascites. Vascular endothelial growth factor (or vascular permeability factor) is an important factor that promotes ascites accumulation.

  • The motility and invasive behaviour of ovarian carcinoma cells are regulated by a repertoire of signalling pathways, several components of which have been evaluated as therapeutic targets in preclinical models and in clinical trials. The identification of new molecular targets might lead to new therapies.

  • Border cells in the Drosophila melanogaster ovary are motile and invasive somatic cells that share some characteristics with ovarian carcinoma cells. Genetic analysis in this simple organism has resulted in the identification of many proteins that contribute to the timing and guidance of border-cell migration.

  • Based on the work in D. melanogaster, the functions of some mammalian proteins, such as myosin VI, have been tested for their ability to regulate motility of ovarian carcinoma cells.

  • An inhibitor of apoptosis protein has been found to promote border-cell migration, in addition to its well-known function in preventing cell death, highlighting the intimate connection between cell survival and motility.

  • The finding that many molecules that promote cell motility also increase resistance to natural or chemotherapy-induced cell death provides a possible molecular basis for the observation that metastatic disease is more resistant to treatment.

Abstract

Despite considerable efforts to improve early detection, and advances in chemotherapy, metastasis remains a major challenge in the clinical management of ovarian cancer. Studies of new murine models are providing novel insights into the pathophysiology of ovarian cancer, but these models are not readily amenable to genetic screens. Genetic analysis of border-cell migration in the Drosophila melanogaster ovary provides clues that will improve our understanding of ovarian cancer metastasis at the molecular level, and also might lead to potential therapeutic targets.

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Figure 1: Structure of the adult human ovary.
Figure 2: Patterns of spread of ovarian carcinoma.
Figure 3: Crucial steps in the regulation of E-cadherin activity.
Figure 4: Relationship between inhibitor of apoptosis proteins, caspases, apoptotic cell death and cell migration.

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Acknowledgements

We thank our colleagues at the University of Texas MD Anderson Cancer Center and the John Hopkins University School of medicine for valuable discussions.

Author information

Authors and Affiliations

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Correspondence to Denise J. Montell.

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The authors declare no competing financial interests.

Related links

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DATABASES

Entrez Gene

AIB1

CA125

CCL21

CCR7

CXCL12

CXCR4

DIAP1

E-cadherin

FAK

myosin VI

PVF1

STAT3

STAT5

Taiman

VEGFR1

VEGFR2

XIAP

National Cancer Institute

breast cancer

ovarian cancer

Glossary

ASCITES

Accumulation of fluid in the peritoneal cavity.

EPITHELIAL–MESENCHYMAL TRANSITION

A process whereby polarized epithelial cells undergo dynamic cytoskeletal remodelling, lose apical/basal-cell polarity and rigid cell–cell attachments, and thereby acquire an irregular, fibroblast-like, mesenchymal morphology.

CHEMOKINES

Small, cytokine-like proteins that are best known for their ability to control leukocyte chemotaxis and recruitment to sites of inflammation.

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Naora, H., Montell, D. Ovarian Cancer Metastasis: Integrating insights from disparate model organisms. Nat Rev Cancer 5, 355–366 (2005). https://doi.org/10.1038/nrc1611

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