Abstract
Cigarette smoking is the number one risk factor for bladder cancer development and epidemiological data suggest that nearly half of all bladder cancer patients have a history of smoking. In addition to stimulating the growth of a primary tumor, it has been shown that there is a correlation between smoking and tumor metastasis. Platelet activating factor (PAF) is expressed on the cell surface of the activated endothelium and, through binding with the PAF-receptor (PAF-R), facilitates transendothelial migration of cells in the circulation (McHowat et al. Biochemistry 40:14921-14931; 2001). In this study, we show that the exposure of bladder cancer cells to cigarette smoke extract (CSE) results in increased PAF accumulation and increased expression of the PAF-R. Furthermore, treatment with CSE increases adherence of bladder cancer cells to bladder endothelial cells and could be abrogated by pretreatment with ginkgolide B. Immunohistochemical analysis of tumor biopsy samples from bladder cancer patients who smoked revealed increased PAF and the PAF-R in tumor regions when compared to normal tissue. These data highlight a pathway in bladder cancer that is influenced by CSE which could facilitate primary tumor growth and increase metastatic potential. Targeting of the PAF-PAFR interaction could serve as a beneficial therapeutic target for managing further growth of a developing tumor.