Exosomes Play Role in Bladder Cancer Metastasis

Researchers at Loyola University in Chicago have shown that exsomes isolated from invasive bladder cancer cell-conditioned media, or from patient urine or bladder barbotage samples, play a role in epithelial-to-mesenchymal transition (EMT), which is a biological process in which epithelial cells lose their epithelial characteristics and acquire a migratory, mesenchymal phenotype. In EMT, epithelial cells lose their cell polarity and cell–cell adhesion and gain migratory and invasive properties to to become mesenchymal stem cells. EMT has been implicated in the initiation of metastasis for cancer progression. The Loyola researchers conclude that their research represents both a new insight into the role of exosomes in transition of bladder cancer into invasive disease, as well as an introduction to a new platform for exosome research in urothelial cells. The new Loyala work was published online on August 17, 2015 in an open-access article in Oncogenesis. The article is titled “Urothelial Cells Undergo Epithelial-to-Mesenchymal Transition after Exposure to Muscle Invasive Bladder Cancer Exosomes.” According to the Loyala authors, “Bladder cancer is the fourth most common noncutaneous malignancy in the United States. Non-muscle-invasive bladder cancer accounts for approximately 70% of newly diagnosed bladder cancer cases, with the remaining 30% being muscle-invasive bladder cancer (MIBC). Although non-muscle-invasive bladder cancer patients have a high survival rate, the recurrence rate is high, and 10–20% of these patients progress to MIBC. Although fewer patients are initially diagnosed with MIBCs, they are responsible for the vast majority of bladder cancer-specific deaths.” The authors noted that prior research has demonstrated that exosomes have a role in cancer biology by promoting survival and growth of disseminated tumor cells; enhancing invasiveness; promoting angiogenesis, migration and tumor cell viability and inhibiting tumor cell apoptosis. Source – bioquicknews

MIBC exosomes decrease expression and alter localization of E-cadherin and β-catenin in urothelial cells. (a) Representative western blotting of E-cadherin expression in urothelial cells after 48 h of treatment with PBS or MIBC exosomes. The bar graph shows the quantitation of E-cadherin expression from four experiments. (b) Representative western blotting of β-catenin expression in urothelial cells after 48 h of treatment with PBS or MIBC exosomes. The bar graph shows the quantitation of β-catenin expression from four experiments. (c, d). Confocal microscopy images of β-catenin and E-cadherin expression and localization in urothelial cells treated with PBS or MIBC exosomes for (c) 24 or (d) 48 h. Confocal microscopy was performed at least three times. A representative image is shown. Scale bar=20 μm. DAPI, 4,6-diamidino-2-phenylindole.