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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Extracellular vesicles produced by NFAT3-expressing cells hinder tumor growth and metastatic dissemination
Lívia Cardoso Bueno de Camargo1, Frédéric Guaddachi1, David Bergerat2
1Université de Paris, Research Saint Louis Institute (IRSL), INSERM HIPI U976, F-75010, Paris, France.
Abstract:
Metastases are the main cause of cancer-induced deaths worldwide. To block tissue invasion, development of extracellular vesicles (EVs) as therapeutic carriers, appears as an exciting challenge. To this aim, we took advantage of the anti-invasive function of NFAT3 transcription factor we identified previously in breast cancer and addressed the opportunity to transfer this inhibitory function by EVs. We show here that EVs produced by poorly invasive NFAT3-expressing breast cancer cell lines are competent to block in vitro invasion of aggressive cancer cells from different origins and, in cooperation with macrophages, inhibit cell proliferation and induce apoptosis. Moreover, this inhibitory effect can be improved by overexpression of NFAT3 in the EVs-producing cells. These results were extended in a mouse breast cancer model, with clear impact of inhibitory EVs on tumor growth and metastases spreading. This work identifies EVs produced by NFAT3-expressing breast cancer cells as an anti-tumoral tool to tackle cancer development and metastases dissemination.
Insights
Extracellular vesicles (EVs) from breast cancer cells expressing NFAT3 can block cancer invasion and metastasis. Overexpressing NFAT3 enhances this anti-tumoral effect, offering a novel therapeutic strategy against cancer spread.
Area of Science:
- Oncology
- Cell Biology
- Nanomedicine
Background:
- Metastasis is a primary driver of cancer mortality globally.
- Extracellular vesicles (EVs) are being explored as therapeutic delivery systems.
- The NFAT3 transcription factor exhibits anti-invasive properties in breast cancer.
Purpose of the Study:
- To investigate the potential of NFAT3-expressing EVs as a therapeutic tool against cancer invasion and metastasis.
- To evaluate the efficacy of EVs derived from NFAT3-expressing cells in inhibiting cancer cell aggressiveness.
- To assess the impact of NFAT3 overexpression in EVs on their anti-tumoral functions.
Main Methods:
- Generation of extracellular vesicles (EVs) from breast cancer cell lines with varying NFAT3 expression levels.
- In vitro assessment of EV-mediated inhibition of cancer cell invasion across different cancer types.
- In vivo evaluation of inhibitory EVs in a mouse breast cancer model to assess tumor growth and metastasis.
- Analysis of EV effects on cancer cell proliferation and apoptosis, including interactions with macrophages.
Main Results:
- EVs from poorly invasive, NFAT3-expressing breast cancer cells effectively blocked in vitro invasion of aggressive cancer cells.
- These EVs, in conjunction with macrophages, inhibited cancer cell proliferation and induced apoptosis.
- Overexpression of NFAT3 in EV-producing cells amplified the observed anti-invasive and anti-proliferative effects.
- In vivo studies demonstrated that inhibitory EVs significantly reduced tumor growth and metastasis spreading in a mouse model.
Conclusions:
- Extracellular vesicles derived from NFAT3-expressing breast cancer cells represent a promising anti-tumoral therapeutic strategy.
- NFAT3-expressing EVs can effectively inhibit cancer cell invasion, proliferation, and metastasis.
- This approach offers a novel method for developing targeted therapies to combat cancer dissemination and improve patient outcomes.
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