Exosomes from human colorectal cancer induce a tumor-like behavior in colonic mesenchymal stromal cells

Abstract

BackgroundCancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression.ResultsCRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes.Materials and MethodsTissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression.ConclusionsCRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

“…Similar results were obtained from IGROV-1, with cisplatin EVs increasing invasiveness by about 5-fold (p = 0.042) (figure 2B). Various studies have shown that EVs can induce an invasive and motile phenotype in recipient cells (63)(64)(65). Our results suggest that, at least in the case of A2780 and IGROV1 cells, the EVs released under normal conditions cannot induce greater levels of invasion when added to cells.…”

Effect of miR-204&211 and RUNX2 control on the fate of human mesenchymal stromal cells

“…Furthermore, stress hematopoiesis, as known, can take place in ectopic sites in Cooley's anemia leading to facial deformity. MSC supporting activity in tissue specific niches for highly demanded lineages, like the hematopoietic and the intestinal epithelia, might allow permissive cross-lineage colonization, as indicated by their functional deployment by adenocarcinoma cells [19], or BM diffusing neuroblastomas. We could thus speculate that some circulating white hematopoietic precursor might, when necessary, utilize peri-cryptal myofibroblasts, as nurturing pseudo-crypt for a local quick expansion [21].…”

Exosomes: New insights into cancer mechanisms

“…Also, they suggested that inhibition of tumor exosomes releasing could be a therapeutic way to interfere with tumor growth. 90 EGFRvIII is expressed in a kind of glioblastoma and its expression is detectable in serum exosomes. This finding helps glioblastoma patients to avoid invasive biopsy of the brain tumor, because the diagnosis of EGFR status in the blood sample provides information about the nature of the disease.…”