Increased exposure to bacterial antigen RpL7/L12 in early stage colorectal cancer patients

Abstract

BACKGROUND:Intestinal bacteria have long been implicated in colorectal cancer pathology, and many reports point to a close linkage between Streptococcus bovis biotype I (recently renamed Streptococcus gallolyticus) infections and tumors of the human colon. This work aims to investigate the humoral immune response to this bacterium during different stages of colorectal cancer. METHODS: The presence of serum antibodies against S. bovis antigen RpL7/L12, previously assigned as a potential diagnostic antigen, was evaluated in Dutch (n ¼ 209) and American (n ¼ 112) populations using a newly developed enzyme-linked immunosorbent assay. RESULTS: The analyses consistently showed that an immune response against this bacterial antigen was increased in polyp patients and stage I/II colorectal cancer patients as compared with asymptomatic individuals. This was not paralleled by increased antibody production to endotoxin, an intrinsic cell wall component of the majority of intestinal bacteria, which implies that the humoral immune response against RpL7/L12 is not a general phenomenon induced by the loss of colonic barrier function. Notably, increased anti-RpL7/L12 levels were not or were only mildly detected in late stage colorectal cancer patients having lymph node or distant metastasis. CONCLUSIONS: These findings are indicative of an increased exposure to antigen RpL7/L12 during early stages of colon carcinogenesis and suggest that intestinal bacteria such as S. bovis constitute a risk factor for the progression of premalignant lesions into early stage carcinomas. Clearly, the current findings emphasize the necessity for further studies on the possible etiologic relationship between intestinal bacteria and human colorectal cancer. Cancer 2010;116:4014-22.

Genomics, evolution, and molecular epidemiology of the Streptococcus bovis / Streptococcus equinus complex (SBSEC)

“…Furthermore, such antigen profiles of Sgg were found to be clearly associated with CRC already present at early polyp status suggesting early involvement of Sgg into the tumour environment (Tjalsma et al, 2006). Major protein antigens of Sgg were identified as HlpA and Rp L7/L12 (Boleij et al, 2010;Tjalsma et al, 2007;Tjalsma et al, 2006), in addition to two unidentified antigens of 22 and 30 kDa size (Garza-González et al, 2012), suggesting further potential for diagnostic tools to detect SBSEC.…”

Bacterial Responses to a Simulated Colon Tumor Microenvironment

“…Proteome and metabolome analyses point toward the increased utilization of glucose and its metabolites together with the amino acid alanine by S. gallolyticus, suggesting that these CRC metabolites are of particular importance for the observed growth advantage. It can be envisaged that this phenomenon may be one of the molecular mechanisms that supports the high incidence of S. gallolyticus infections in CRC patients (16,28). Below, we will speculate how such a mechanism could have its place in the complex ecosystem of the gut.…”

Organ Microbiota in Cancer Development: The Holy Grail of Biological Carcinogenesis

“…According to the data of Sobhani et al ( 2011 ) , colorectal cancer patients have an elevated concentration of Bacteroides and Prevotella in their feces. Boleij et al ( 2010 ) revealed the immune response to RpL7/L12 antigen of Streptococcus bovis is more enhanced in subjects with polyps and with I/II colorectal cancer stages in comparison with asymptomatic individuals. Scanlan et al ( 2008 ) found that the microbiota of colorectal cancer subjects and patients with polyposis is less stable in time and has greater diversity compared to the micro fl ora of healthy controls.…”