Uptake of circulating extracellular vesicles from rectal cancer patients and differential responses by human monocyte cultures. Issue 3 (8th February 2021)

• Record Type: Journal Article
• Authors: Bjørnetrø, Tonje; Steffensen, Lilly Alice; Vestad, Beate; Brusletto, Berit Sletbakk; Olstad, Ole Kristoffer; Trøseid, Anne‐Marie; Aass, Hans Christian Dalsbotten; Haug, Kari Bente Foss; Llorente, Alicia; Bøe, Stig Ove; Lång, Anna; Samiappan, Rampradeep; Redalen, Kathrine Røe; Øvstebø, Reidun; Ree, Anne Hansen
• Is Part Of: FEBS open bio. Volume 11:Issue 3(2021)
• Page Start: 724
• Page End: 740
• Publication Date: 2021-02-08
• Subjects: colorectal cancer -- extracellular vesicles -- inflammation -- monocytes -- tumor microenvironment; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13098
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Extracellular vesicles (EVs) released by tumor cells can directly or indirectly modulate the phenotype and function of the immune cells of the microenvironment locally or at distant sites. The uptake of circulating EVs and the responses by human monocytes in vitro may provide new insights into the underlying biology of the invasive and metastatic processes in cancer. Although a mixed population of vesicles is obtained with most isolation techniques, we predominantly isolated exosomes (small EVs) and microvesicles (medium EVs) from the SW480 colorectal cancer cell line (established from a primary adenocarcinoma of the colon) by sequential centrifugation and ultrafiltration, and plasma EVs were prepared from 22 patients with rectal adenoma polyps or invasive adenocarcinoma by size‐exclusion chromatography. The EVs were thoroughly characterized. The uptake of SW480 EVs was analyzed, and small SW480 EVs were observed to be more potent than medium SW480 EVs in inducing monocyte secretion of cytokines. The plasma EVs were also internalized by monocytes; however, their cytokine‐releasing potency was lower than that of the cell line‐derived vesicles. The transcriptional changes in the monocytes highlighted differences between adenoma and adenocarcinoma patient EVs in their ability to regulate biological functions, whereas the most intriguing changes were found in monocytes receiving EVs from patients with metastatic compared with localized cancer. Abstract : Plasma EVs may mediate the interplay between the tumor and patient's immune responses in cancer dissemination. Isolated plasma EVs from rectal cancer patients were internalized by cultured human monocytes and caused cytokine release. Transcriptional responses associated with cancer progression were stronger and had higher biological complexity in monocytes given EVs from patients with metastasis than from patients with localized cancer.