Journal
CLINICAL & EXPERIMENTAL METASTASIS
Volume 39, Issue 2, Pages 291-301Publisher
SPRINGER
DOI: 10.1007/s10585-021-10136-5
Keywords
Ovarian cancer; Integrins; Metastasis; Cell adhesion; Tumor progression
Categories
Funding
- Canadian Institutes for Health Research [136836]
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Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in the developed world, with a unique metastasis process involving cell detachment and formation of spheroids. Integrins, a family of cell adhesion receptors, play a crucial role in EOC metastasis impacting various steps of cancer progression, suggesting a potential therapeutic target for advanced EOC.
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in the developed world. EOC metastasis is unique since malignant cells detach directly from the primary tumor site into the abdominal fluid and form multicellular aggregates, called spheroids, that possess enhanced survival mechanisms while in suspension. As such, altered cell adhesion properties are paramount to EOC metastasis with cell detachment from the primary tumor, dissemination as spheroids, and reattachment to peritoneal surfaces for secondary tumor formation. The ability for EOC cells to establish and maintain cell-cell contacts in spheroids is critical for cell survival in suspension. Integrins are a family of cell adhesion receptors that play a crucial role in cell-cell and cell-extracellular matrix interactions. These glycoprotein receptors regulate diverse functions in tumor cells and are implicated in multiple steps of cancer progression. Altered integrin expression is detected in numerous carcinomas, where they play a role in cell migration, invasion, and anchorage-independent survival. Like that observed for other carcinomas, epithelial-mesenchymal transition (EMT) occurs during metastasis and integrins can function in this process as well. Herein, we provide a review of the evidence for integrin-mediated cell adhesion mechanisms impacting steps of EOC metastasis. Taken together, targeting integrin function may represent a potential therapeutic strategy to inhibit progression of advanced EOC.
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