Exosomal αvβ6 integrin is required for monocyte M2 polarization in prostate cancer.
Publication/Presentation Date
9-1-2018
Abstract
Therapeutic approaches aimed at curing prostate cancer are only partially successful given the occurrence of highly metastatic resistant phenotypes that frequently develop in response to therapies. Recently, we have described αvβ6, a surface receptor of the integrin family as a novel therapeutic target for prostate cancer; this epithelial-specific molecule is an ideal target since, unlike other integrins, it is found in different types of cancer but not in normal tissues. We describe a novel αvβ6-mediated signaling pathway that has profound effects on the microenvironment. We show that αvβ6 is transferred from cancer cells to monocytes, including β6-null monocytes, by exosomes and that monocytes from prostate cancer patients, but not from healthy volunteers, express αvβ6. Cancer cell exosomes, purified via density gradients, promote M2 polarization, whereas αvβ6 down-regulation in exosomes inhibits M2 polarization in recipient monocytes. Also, as evaluated by our proteomic analysis, αvβ6 down-regulation causes a significant increase in donor cancer cells, and their exosomes, of two molecules that have a tumor suppressive role, STAT1 and MX1/2. Finally, using the Pten
Volume
70
First Page
20
Last Page
35
ISSN
1569-1802
Published In/Presented At
Lu, H., Bowler, N., Harshyne, L. A., Craig Hooper, D., Krishn, S. R., Kurtoglu, S., Fedele, C., Liu, Q., Tang, H. Y., Kossenkov, A. V., Kelly, W. K., Wang, K., Kean, R. B., Weinreb, P. H., Yu, L., Dutta, A., Fortina, P., Ertel, A., Stanczak, M., Forsberg, F., … Languino, L. R. (2018). Exosomal αvβ6 integrin is required for monocyte M2 polarization in prostate cancer. Matrix biology : journal of the International Society for Matrix Biology, 70, 20–35. https://doi.org/10.1016/j.matbio.2018.03.009
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
29530483
Department(s)
Administration and Leadership
Document Type
Article