Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis).
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.
Biarc
Jordane
J
Inserm UMR-S 392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France.
Nguyen
Isabelle S
IS
Pini
Annelise
A
Gossé
Francine
F
Richert
Sophie
S
Thiersé
Danielle
D
Van Dorsselaer
Alain
A
Leize-Wagner
Emmanuelle
E
Raul
Francis
F
Klein
Jean-Paul
JP
Schöller-Guinard
Marie
M
D000818:Animals; D015153:Blotting, Western; D018938:Caco-2 Cells; D002273:Carcinogens; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation; D016209:Interleukin-8 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D013058:Mass Spectrometry; D008565:Membrane Proteins; D009092:Mucous Membrane / Q000473:pathology; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D020543:Proteome; D051381:Rats; D016985:Streptococcus bovis / Q000378:metabolism*; D013347:Subcellular Fractions; D013997:Time Factors
D002273:Carcinogens; D004791:Enzyme Inhibitors; D016209:Interleukin-8; D007527:Isoenzymes; D008565:Membrane Proteins; D020543:Proteome; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone