Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S.bovis)

Carcinogenesis. 2004 Aug;25(8):1477-84. doi: 10.1093/carcin/bgh091. Epub 2004 Jan 23.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Caco-2 Cells
  • Carcinogens*
  • Cell Differentiation
  • Cell Line, Tumor
  • Colonic Neoplasms / metabolism
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Electrophoresis, Gel, Two-Dimensional
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrogen-Ion Concentration
  • Inflammation
  • Interleukin-8 / metabolism
  • Isoenzymes / metabolism
  • Mass Spectrometry
  • Membrane Proteins
  • Mucous Membrane / pathology
  • Phosphorylation
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Proteome
  • Rats
  • Streptococcus bovis / metabolism*
  • Subcellular Fractions
  • Time Factors


  • Carcinogens
  • Enzyme Inhibitors
  • Interleukin-8
  • Isoenzymes
  • Membrane Proteins
  • Proteome
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone