BERKELEY, CA (UroToday.com) - Microvesicles have gained considerable attention recently as mediators of cell-cell communication. Of importance, the protein content of exosomes, specifically, has been shown to be cargo sorted.[1, 2, 3] It is reasonable, therefore, for us to believe that exosomes facilitate a pre-defined protein courier mechanism which also mules genetic material between cells in a microenvironment that is perhaps even systemic.
We have thus profiled the protein cargo of exosomes using proteomic mass spectrometry and carried out comparative analysis of those derived from a panel of prostate cancer cell lines (one benign cell line was also included in our analysis).[4] As a result, we have been able to demonstrate that tumour-derived exosomes provide biomarker-enriched samples which may yield protein biomarkers, in addition to numerous mRNA and miRNA transcript-related biomarkers currently highlighted in the scientific literature. It is important to recognize that we have merely scratched the surface in demonstrating also that exosomes derived from prostate tumour cells transfer to non-identical cells in vitro.[4]
Numerous in vitro studies demonstrate that exosomes mediate a phenotypic change in surrounding cells from a variety of origins, akin to an assimilation process.[5] In the case of tumour cells for which constitutive activation and/or suppression of pathways lead to dysregulation of normal growth control, this idea is alarming. We now start to question whether normal adjacent cells assimilate to become cancerous in response to bombardment by microvesicular signalling cargo, their membranes slowly being infiltrated by an aberrant enrichment of lipid raft signalling hubs bearing cell surface receptors such as epidermal growth factor receptor (EGFR). If so, how far beyond the local microenvironment does the assimilation extend, and as we discover that exosomes could be priming metastatic sites for circulating micro-metastases,[5] are we starting to discover a landscape in cancer research in which no micro-foci is an island?
Exciting times, indeed.
References:
- Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitindependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106, 145–155 (2001).
- Hicke, L. A new ticket for entry into budding vesicles — ubiquitin. Cell 106, 527–530 (2001).
- Thery, C., Zitvogel, L., and Amigorena, S. Exosomes: Composition, Biogenesis and Function. Nat Rev Immunol 2, 569-579 (2002).
- Hosseini-Beheshti E, Pham S, Adomat H, Li N, Tomlinson Guns ES. Exosomes as biomarker enriched microvesicles: Characterization of exosomal proteins derived from a panel of prostate cell Lines with distinct AR phenotypes. Mol Cell Proteomics 11: 863-885 (2012).
- Peinado H, Alečković M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, García-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 18(6):883-91 (2012).
Written by:
Emma S. Tomlinson Guns, PhD and Elham Hosseini-Beheshti, PhD candidate as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
The Vancouver Prostate Centre, University of British Columbia; Vancouver, British Columbia, V6H 3Z6; Canada
More Information about Beyond the Abstract