Investigation into the controversial association of Streptococcus gallolyticus with colorectal cancer and adenoma

Abstract

BackgroundThe seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-κB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis.MethodsELISA was used to measure IgG antibodies of S. gallolyticus and B. fragilis in sera of 50 colorectal cancer, 14 colorectal adenoma patients, 30 age- and sex- matched apparently healthy volunteers (HV) and 30 age- and sex- matched colonoscopically-proven tumor-free control subjects. NF-κB and IL-8 mRNA expression was evaluated in tumorous and non-tumorous tissue sections of carcinoma and adenoma patients in comparison with that of control subjects by using in situ hybridization assay.ResultsColorectal cancer and adenoma patients were associated with higher levels of serum S. gallolyticus IgG antibodies in comparison with HV and control subjects (P < 0.05) while no similar association was found with serum IgG antibodies of B. fragilis (P > 0.05). ELISA cutoff value for the seropositivity of S. gallolyticus IgG was calculated from tumor-free control group. The expression of NF-κB mRNA was higher in tumorous than non-tumorous tissue sections of adenoma and carcinoma, higher in carcinoma/adenoma sections than in control subjects, higher in tumorous sections of carcinoma than in adenoma patients, and higher in S. gallolyticus IgG seropositive than in seronegative groups in both tumorous and non-tumorous sections (P < 0.05). IL-8 mRNA expression in tumorous sections of adenoma and carcinoma was higher than in non-tumorous sections, higher in carcinoma/adenoma than in control subjects, and higher in S. gallolyticus IgG seropositive than in seronegative groups in tumorous rather than non-tumorous sections (P < 0.05).ConclusionS. gallolyticus most likely plays an essential role in the oncogenic progression of normal colorectal mucosa to adenoma and to CRC. This promoting/propagating role of S. gallolyticus might take place by utilizing certain inflammatory, anti-apoptotic, and angiogenic factors of transformation including NF-κB and IL-8.

Streptococcus bovis/gallolyticus Induce the Development of Colorectal Cancer

“…However, surprisingly, another study (Devis et al, 1989) found that the association between S. bovis/gallolyticus and adenoma was more evident than that with colorectal cancer; they r e p o r t e d t h a t 3 6 % o f p o s i t i v e b l o o d c u l t u r e s o f S. bovis/gallolyticus were found in proliferative lesions (15% of cancers and 21% of adenomas). A recent study (Abdulamir et al, 2009) supported this concept showing that the level of S. bovis/gallolyticus IgG antibodies in adenoma patients is much higher than in both colorectal cancer patients and control subjects. However, other reports did not reveal the same thing.…”

“…Nevertheless, the relationship between colorectal bacterial infection and the progressive development of malignant disease in pre-neoplastic adenomatous polyps was supported by recent reports (Abdulamir et al, 2009;Kahveci et al, 2010;Murinello et al, 2006). Interestingly, benign lesions (diverticulosis, inflammatory bowel disease, cecal volvulus, perirectal abscess hemorrhoids, benign polyps) were found to be mildly associated with intestinal bacterial infections such as S. bovis/gallolyticus while a strong relationship between more malignant diseases of the colon (cancer and neoplastic polyps) and S. bovis/gallolyticus was found (Abdulamir et al, 2009;Burns et al, 1985;Klein et al, 1979;Nielsen et al, 2007;Reynolds et al, 1983;Smaali et al, 2008). It was also revealed that S. bovis/gallolyticus septicemia and/or endocarditis is selectively related to the presence of villous or tubulovillous adenomas in the large intestine (Fagundes et al, 2000;Smaali et al, 2008).…”

“…Contrary to the more commonly reported association between S. bovis/gallolyticus bacteremia and colorectal cancer, a link to pre-neoplastic adenomatous polyps was less frequently reported (Burns et al, 1985;Ellmerich et al, 2000a). Nevertheless, the relationship between colorectal bacterial infection and the progressive development of malignant disease in pre-neoplastic adenomatous polyps was supported by recent reports (Abdulamir et al, 2009;Kahveci et al, 2010;Murinello et al, 2006). Interestingly, benign lesions (diverticulosis, inflammatory bowel disease, cecal volvulus, perirectal abscess hemorrhoids, benign polyps) were found to be mildly associated with intestinal bacterial infections such as S. bovis/gallolyticus while a strong relationship between more malignant diseases of the colon (cancer and neoplastic polyps) and S. bovis/gallolyticus was found (Abdulamir et al, 2009;Burns et al, 1985;Klein et al, 1979;Nielsen et al, 2007;Reynolds et al, 1983;Smaali et al, 2008).…”

“…This provided evidence for a possible important role of S. gallolyticus in the carcinogenesis of colorectal cancer from pre-malignant polyps. In addition, it was also found that NF-κB and IL-8 rather than other transformation factors p21, p27 and p53 act as important mediators for the S. gallolyticus-associated transformation of adenoma to carcinoma (Abdulamir et al, 2009). Moreover, it was concluded that NF-κB exerts most probably a promoting carcinogenic effect and IL-8 exerts mainly an angiogenic-based propagating effect on colorectal mucosal cells (Abdulamir et al, 2009).…”

“…In addition, it was also found that NF-κB and IL-8 rather than other transformation factors p21, p27 and p53 act as important mediators for the S. gallolyticus-associated transformation of adenoma to carcinoma (Abdulamir et al, 2009). Moreover, it was concluded that NF-κB exerts most probably a promoting carcinogenic effect and IL-8 exerts mainly an angiogenic-based propagating effect on colorectal mucosal cells (Abdulamir et al, 2009). In addition, a more recent study done by our team showed a direct and active role of S. bovis/gallolyticus in colorectal cancer development through inflammation-based sequel of tumor development or propagation via IL-1, COX-2, and IL-8 (Abdulamir et al, 2010).…”