Communication Dans Un Congrès Année : 2022

Unraveling the role of CD133 in breast cancer-Extracellular Vesicles in invasion and metastasis

Gisela D’angelo
Mireia Gomez-Duro
Sarah Watson

Résumé

The spread of cancer cells from the primary tumor into surrounding tissues and metastasis to distant organs is the primary cause of cancer morbidity and mortality. Recent data suggest that cancer cells release extracellular vesicles (EVs), membranous nanocarriers containing proteins and genetic material, which may stimulate the invasion and dissemination of tumor cells to target cells. The invasive and metastatic character of several cancer types is associated with the presence of CD133, predicting poor outcomes in cancer patients. CD133 is among one the molecular signature of EVs. The major goal is to correlate the expression of CD133 in breast cancer cells, to EV secretion, and their EV-mediated invasive and metastatic properties with a long-term goal for the development of innovative EV-based therapeutic approaches. EVs from two triple-negative breast cancer (TNBC) cell lines (MDA-MB-468 and MDA-MB-231) and one hormone-dependent cell line (MCF-7) were isolated by size exclusion chromatography (SEC) and ultracentrifugation (UC), characterized by immunoblotting, NTA, Macsplex, TEM, and IEM to evaluate their size, morphology, and composition. The three cell lines secrete a heterogeneous population of EVs, consisting of large- (150-250nm) and small EVs (50-150nm), the latter being more abundant. Immunoblot analysis reveals the presence of EV-specific markers (CD9, CD81, CD63, Alix, Tsg101) and CD133 in both populations. However, expression levels are higher in MDA-MB-468-EVs. Moreover, in MDA-MB-468-EVs, CD9 and CD81/CD133 expressions are more abundant in large and small-EVs respectively. Our results indicate that the expression of CD133 in EVs doesn’t equally occur in all cell lines, suggesting that this may influence their metastatic capacity and tumor development. Moreover, our preliminary data indicate that TNBC-derived EVs, bearing CD133, promote branching and sprouting in endothelial cells, a key feature in cancer invasion compared with the positive control VEGF. We are currently evaluating in vitro the function of EVs on migration and on epithelial-mesenchymal transition (EMT), potentially related to the metastatic capacity of cancer cells.

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Dates et versions

hal-04343912 , version 1 (14-12-2023)

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  • HAL Id : hal-04343912 , version 1

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Gisela D’angelo, Mireia Gomez-Duro, Sarah Watson, Graca Raposo. Unraveling the role of CD133 in breast cancer-Extracellular Vesicles in invasion and metastasis. 5th FSEV meeting, Guillaume van Niel, Oct 2022, PAris, France. ⟨hal-04343912⟩
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