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Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells

1
Centre for Molecular Biology “Severo Ochoa” (CSIC-UAM), Cell-Cell Communication & Inflammation Unit, 28049 Madrid, Spain
2
Department of Molecular Biology, Faculty of Sciences, Universidad Autónoma de Madrid, 28049 Madrid, Spain
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Department of Immunology, Ophthalmology and Otorhinolaryngology, School of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
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Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12), 28041 Madrid, Spain
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Department of Obstetrics and Gynecology, Hospital Universitario Quironsalud Madrid, 28223 Madrid, Spain
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Instituto de Investigación Sanitaria Hospital La Princesa, 28006 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Alfred King-Yin Lam
Int. J. Mol. Sci. 2021, 22(18), 9938; https://doi.org/10.3390/ijms22189938
Received: 2 September 2021 / Accepted: 10 September 2021 / Published: 14 September 2021
(This article belongs to the Section Molecular Oncology)
Approximately 25% of colorectal cancer (CRC) patients develop peritoneal metastasis, a condition associated with a bleak prognosis. The CRC peritoneal dissemination cascade involves the shedding of cancer cells from the primary tumor, their transport through the peritoneal cavity, their adhesion to the peritoneal mesothelial cells (PMCs) that line all peritoneal organs, and invasion of cancer cells through this mesothelial cell barrier and underlying stroma to establish new metastatic foci. Exosomes produced by cancer cells have been shown to influence many processes related to cancer progression and metastasis. In epithelial ovarian cancer these extracellular vesicles (EVs) have been shown to favor different steps of the peritoneal dissemination cascade by changing the functional phenotype of cancer cells and PMCs. Little is currently known, however, about the roles played by exosomes in the pathogenesis and peritoneal metastasis cascade of CRC and especially about the molecules that mediate their interaction and uptake by target PMCs and tumor cells. We isolated exosomes by size−exclusion chromatography from CRC cells and performed cell-adhesion assays to immobilized exosomes in the presence of blocking antibodies against surface proteins and measured the uptake of fluorescently-labelled exosomes. We report here that the interaction between integrin α5β1 on CRC cells (and PMCs) and its ligand ADAM17 on exosomes mediated the binding and uptake of CRC-derived exosomes. Furthermore, this process was negatively regulated by the expression of tetraspanin CD9 on exosomes. View Full-Text
Keywords: exosomes; extracellular vesicles; peritoneal metastasis; colorectal cancer; adhesion molecules; ADAM17/TACE; integrin α5β1; tetraspanin CD9 exosomes; extracellular vesicles; peritoneal metastasis; colorectal cancer; adhesion molecules; ADAM17/TACE; integrin α5β1; tetraspanin CD9
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MDPI and ACS Style

Cardeñes, B.; Clares, I.; Toribio, V.; Pascual, L.; López-Martín, S.; Torres-Gomez, A.; Sainz de la Cuesta, R.; Lafuente, E.M.; López-Cabrera, M.; Yáñez-Mó, M.; Cabañas, C. Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells. Int. J. Mol. Sci. 2021, 22, 9938. https://doi.org/10.3390/ijms22189938

AMA Style

Cardeñes B, Clares I, Toribio V, Pascual L, López-Martín S, Torres-Gomez A, Sainz de la Cuesta R, Lafuente EM, López-Cabrera M, Yáñez-Mó M, Cabañas C. Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells. International Journal of Molecular Sciences. 2021; 22(18):9938. https://doi.org/10.3390/ijms22189938

Chicago/Turabian Style

Cardeñes, Beatriz, Irene Clares, Víctor Toribio, Lucía Pascual, Soraya López-Martín, Alvaro Torres-Gomez, Ricardo Sainz de la Cuesta, Esther M. Lafuente, Manuel López-Cabrera, María Yáñez-Mó, and Carlos Cabañas. 2021. "Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells" International Journal of Molecular Sciences 22, no. 18: 9938. https://doi.org/10.3390/ijms22189938

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