The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination

Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peri...

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Bibliographic Details
Published in:Cancers 2021-05, Vol.13 (10), p.2505
Main Authors: Serratì, Simona, Porcelli, Letizia, Fragassi, Francesco, Garofoli, Marianna, Di Fonte, Roberta, Fucci, Livia, Iacobazzi, Rosa Maria, Palazzo, Antonio, Margheri, Francesca, Cristiani, Grazia, Albano, Anna, De Luca, Raffaele, Altomare, Donato Francesco, Simone, Michele, Azzariti, Amalia
Format: Article
Language:English
Subjects:
Antibodies
Antitumor activity
Apoptosis
Ascites
Biomarkers
Cancer
Caspase-3
CD44 antigen
Cell activation
Colorectal cancer
Colorectal carcinoma
Experiments
Extracellular vesicles
Fibroblasts
Gelatinase A
Invasiveness
Mesenchyme
Metastases
Metastasis
Microenvironments
Ovarian cancer
Patients
Peritoneum
Proteins
Senescence
Surgery
Transforming growth factor-b1
Tumor cells
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Summary:Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-β1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13102505