Positive Loop of Smoking and Extracellular Vesicles in Bladder Field Cancerization
Abstract
Our research project addresses the FY18 PRCRP Topic Area of Bladder Cancer. Bladder cancer (BC) is one of the most common cancers in American men. Approximately 70% to 80% of patients with BC present with non-muscle invasive BC. Although the management of non-muscle invasive BC has improved during the past few years, the high rate of recurrence of non-muscle invasive BC surpasses that of all other cancers, and understanding the causes of disease recurrence might lead to developing clinical strategies to manage patients with non-muscle invasive disease. Extracellular vesicles (EVs), small vesicles secreted by all cells, carry bio-information and serve as key messengers to communicate with cells locally and at distance through circulation. Cancer cells secrete substantially greater numbers of EVs than normal cells. They participate in many cell activities and can be induced by cellular stress response. We have shown that EVs derived from BC cells (BCEVs) and patients are loaded with oncogenic molecules that can be taken up by recipient normal cells and alter their behaviors, and ultimately, can transform the normal cells to become cancers. Cigarette smoking is the most well-known carcinogen for BC, and smokers have a three-fold higher chance of developing BC. Approximately 50% of BC patients are cigarette smokers. While E-cigarettes (E-cigs) may be safer than traditional cigarettes, the composition of E-cigs is complex and unregulated. Since the population of E-cig users is rising rapidly, more research is needed to investigate the carcinogenic properties of E-cigs and flavors and the link between E-cigs and BC. In this proposal, we study the transformation of normal urothelial cells induced by BCEVs in response to cigarette smoking and E-cigs. It provides a novel mechanism to explain the frequent BC recurrence rate, as well as establishing carcinogenicity of cigarette smoking and E-cigs. The molecular and cellular alterations upon cigarette smoke, Ecigs, and their interaction with BCEVs will be examined. E-cigs became popular less than a decade ago. Data from population-based studies on E-cigs impacts on BC wont become available at least for another decade. Our bladder carcinogenesis model provides a good alternative to examine carcinogenicity of smoke, E-cigs, and BCEVs present in the bladder environment. The majority of U.S. military Veterans are age 55 and older, and BC occurs mainly in older people. Studies have shown that U.S. military Veterans are twice as likely to be diagnosed with BC as the general population. Smoking might be one of the contributing factors, since Veterans have a higher prevalence of smoking than the non-Veteran population. The results may lead to new therapeutic strategies and dispel unsubstantiated claims that E-cigs are safe. The outcome of this study will be beneficial to the general population, but in particular to the military population and Veterans, in view of their higher prevalence of smokers than the non-Veteran population.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910198
Entities
People
- Yi-fen Lee
Organizations
- United States Army
- University of Rochester