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.
Researchers at the Istituto Superiore di Sanità, Italy exposed tissue specific colonic (c)MSCs to primary or metastatic CRC exosomes and analysed them 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.
The researchers found that 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.
Colorectal cancer exosomes increase the migration and invasive ability of colonic MSCs
(A) Phase contrast microscopy images of migration capability of colonic MSCs untreated (CTR) or treated for 72 hours with pCRCexo and graphic of relative migrated cell percentage. 4X magnification. (B) Phase contrast microscopy images of Matrigel™ invasion capability of MSCs treated for 72 hours with pCRCexo and graphic of relative invading cell percentage. 20X magnification. In either A and B figures, cMSCs were stained with crystal violet solution (for details see M&M) and the results were obtained analysing at least 5 fields of each sample. Data are represented as mean ± SD with n = at least three independent sets of experiments (***p ≤ 0.001).
CRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. These results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.