Dataset Information

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

ABSTRACT:

Background

Cancer 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.

Results

CRC 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 methods

Tissue 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.

Conclusions

CRC 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.

SUBMITTER: Lugini L

PROVIDER: S-EPMC5226570 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Lugini Luana L Valtieri Mauro M Federici Cristina C Cecchetti Serena S Meschini Stefania S Condello Maria M Signore Michele M Fais Stefano S

Oncotarget 20160801 31

<h4>Background</h4>Cancer 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.<h4>Results</h4>CRC 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 plas ...[more]

PMID: 27418137

Similar Datasets

Project description:BackgroundExosomes are nanoscale membrane vesicles secreted by both normal and cancer cells, and cancer cell-derived exosomes play an important role in the cross-talk between cancer cells and other cellular components in the tumor microenvironment. Mesenchymal stem cells (MSCs) have tropism for tumors and have been used as tumor-tropic vectors for tumor therapy; however, the safety of such therapeutic use of MSCs is unknown. In this study, we investigated the role of glioma cell-derived exosomes in the tumor-like phenotype transformation of human bone marrow mesenchymal stem cells (hBMSCs) and explored the underlying molecular mechanisms.MethodsThe effect of exosomes from U251 glioma cells on the growth of hBMSCs was evaluated with the CCK-8 assay, KI67 staining, and a cell cycle distribution assessment. The migration and invasion of hBMSCs were evaluated with a Transwell assay. A proteomics and bioinformatics approach, together with Western blotting and reverse transcriptase-polymerase chain reaction, was used to investigate the effect of U251 cell-derived exosomes on the proteome of hBMSCs.ResultsU251 cell-derived exosomes induced a tumor-like phenotype in hBMSCs by enhancing their proliferation, migration, and invasion and altering the production of proteins involved in the regulation of the cell cycle. Moreover, U251 cell-derived exosomes promoted the production of the metastasis-related proteins MMP-2 and MMP-9, glioma marker GFAP, and CSC markers (CD133 and Nestin). The ten differentially expressed proteins identified participated in several biological processes and exhibited various molecular functions, mainly related to the inactivation of glycolysis. Western blotting showed that U251 cell-derived exosomes upregulated the levels of Glut-1, HK-2, and PKM-2, leading to the induction of glucose consumption and generation of lactate and ATP. Treatment with 2-deoxy-D-glucose significantly reversed these effects of U251 cell-derived exosomes on hBMSCs.ConclusionsOur data demonstrate that glioma cell-derived exosomes activate glycolysis in hBMSCs, resulting in their tumor-like phenotype transformation. This suggests that interfering with the interaction between exosomes and hBMSCs in the tumor microenvironment has potential as a therapeutic approach for glioma. ᅟ.

Dataset Information

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

Background

Results

Materials and methods

Conclusions

Publications

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

Similar Datasets

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