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

Abstract

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.

Bacteria, inflammation, and colon cancer

“…In the presence of these proteins, Caco-2 cells exhibited enhanced phosphorylation of MAP kinases. These data suggest that bacterial components possess both proinflammatory properties and procarcinogenic potentials, and support the hypothesis that colonic bacteria can contribute to cancer development, particularly in association with chronic infection/inflammation diseases where these bacterial components might interfere with cell function [41] . Clostridium septicum infections are rare, but are often associated with malignancy.…”

Haematologic Parameters in Metastatic Colorectal Cancer Patients Treated with Capecitabine Combination Therapy

“…Inflammation is thought to contribute to the development and progression of various cancers (Altinoz et al, 2004;Biarc et al, 2004). It is only been in the past decade, however, that the complexities of the tumor inflammatory microenvironment and the host's response to tumor induced inflammatory pathways have begun to be understood, resulting in an improved ability to prevent and treat malignancy.…”

Interleukin‐6 and its receptor in cancer

“…It was suggested in recent studies that inflammation and IL-6/sIL-6R expression play a role in the pathogenesis of colon cancer. 15,62 In cholangiocarcinoma cells, increased IL-6 and myeloid cell leukemia 1 (Mcl-1) expression is a result of silencing of the suppressor of cytokine signaling 3 (SOC-3) gene by methylation. SOCS-3 normally suppresses the IL-6/STAT3 signaling pathway by using a negative feedback loop.…”