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

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Cardeñes, Beatriz and Clares, Irene and Toribio, Víctor and Pascual, Lucía and López Martín, Soraya and Torres Gómez, Álvaro and Sainz de la Cuesta, Ricardo and Lafuente Duarte, Esther M. and López Cabrera, Manuel and Yáñez Mó, María and Cabañas Gutiérrez, Carlos (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 (18). p. 9938. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms22189938




Abstract

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.


Item Type:Article
Uncontrolled Keywords:exosomes; extracellular vesicles; peritoneal metastasis; colorectal cancer; adhesion molecules; ADAM17/TACE; integrin α5β1; tetraspanin CD9
Subjects:Medical sciences > Medicine > Oncology
ID Code:71678
Deposited On:22 Apr 2022 13:25
Last Modified:25 Apr 2022 07:49

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