Carcinogenesis Advance Access originally published online on January 23, 2004
Carcinogenesis 2004 25(8):1477-1484; doi:10.1093/carcin/bgh091
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Carcinogenesis vol.25 no.8 © Oxford University Press 2004; all rights reserved.
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Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis)
1 Inserm UMR-S 392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France and 2 CNRS UMR 7509, CNRS-Université Louis Pasteur, F-67087 Strasbourg Cedex 2, France
3 To whom correspondence should be addressed Email: scholler{at}pharma.u-strasbg.fr
Several studies reported linkage between bacterial infections and carcinogenesis. Streptococcus bovis was traditionally considered as a lower grade pathogen frequently involved in bacteremia and endocarditis. This bacterium became important in human health as it was shown that 25–80% of patients who presented a S.bovis bacteremia had also a colorectal tumor. Moreover, in previous experiments, we demonstrated that S.bovis or S.bovis wall extracted antigens (WEA) were able to promote carcinogenesis in rats. The aim of the present study was: (i) to identify the S.bovis proteins responsible for in vitro pro-inflammatory properties; (ii) to purify them; (iii) to examine their ability to stimulate in vitro IL-8 and COX-2 expression by human colon cancer cells; and (iv) to assess in vivo their pro-carcinogenic potential in a rat model of colon carcinogenesis. The purified S300 fraction, as determined by proteomic analysis, contained 72 protein spots in two-dimensional gel electrophoresis representing 12 different proteins able to trigger human epithelial colonic Caco-2 cells and rat colonic mucosa to release CXC chemokines (human IL-8 or rat CINC/GRO) and prostaglandins E2, correlated with an in vitro over-expression of COX-2. Moreover, these proteins were highly effective in the promotion of pre-neoplastic lesions in azoxymethane-treated rats. In the presence of these proteins, Caco-2 cells exhibited enhanced phosphorylation of the three classes of MAP kinases. Our results show a relationship between the pro-inflammatory potential of S.bovis proteins and their pro-carcinogenic properties, confirming the linkage between inflammation and colon carcinogenesis. These data support the hypothesis that colonic bacteria can contribute to cancer development particularly in chronic infection/inflammation diseases where bacterial components may interfere with cell function.
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