RT Journal Article
T1 Cellular Integrin α5β1 and Exosomal ADAM17 Mediate the Binding and Uptake of Exosomes Produced by Colorectal Carcinoma Cells
A1 Cardeñes, Beatriz
A1 Clares, Irene
A1 Toribio, Víctor
A1 Pascual, Lucía
A1 López Martín, Soraya
A1 Torres Gómez, Álvaro
A1 Sainz de la Cuesta, Ricardo
A1 Lafuente Duarte, Esther M.
A1 López Cabrera, Manuel
A1 Yáñez Mó, María
A1 Cabañas Gutiérrez, Carlos
AB 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.
PB MPDI
SN 1422-0067
YR 2021
FD 2021-09-14
LK https://hdl.handle.net/20.500.14352/4840
UL https://hdl.handle.net/20.500.14352/4840
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)/FEDER
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
DS Docta Complutense
RD 3 may 2024