Increased Exposure to Bacterial Antigen RpL7/L12 in Early Stage Colorectal Cancer Patients
Annemarie Boleij1, Rian Roelofs1, Renée M.J. Schaeps1, Tanja Schülin2, Philippe Glaser3, Dorine W. Swinkels1, Ikuko Kato4, Harold Tjalsma1 Cancer 2010;116:4014-22.
Departments of 1Laboratory Medicine (Clinical Chemistry) and 2Medical Microbiology, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Radboud University Centre for Oncology (RUCO) of the Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; 3Unité de Génomique des Microorganismes Pathogènes, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France; 4Karmanos Cancer Institute, Department of Pathology, Wayne State University, Detroit, MI, USA.
Humoral immune response to bacterium during different stages of CRC:
Intestinal bacteria have been implicated in colorectal cancer (CRC) pathology for a long time and a large number of reports point to a close linkage between Streptococcus gallolyticus infections and tumors of the human colon. This study aimed to investigate the humoral immune response to this bacterium during different stages of CRC.
Presence of serum IgGs against ribosomal protein (Rp) L7/L12 from S. gallolyticus:
To this purpose, the presence of serum IgGs against ribosomal protein (Rp) L7/L12 from S. gallolyticus was evaluated in Dutch and American populations by an in-house developed ELISA assay. RpL7/L12 was previously identified as a candidate diagnostic antigen for CRC. The data consistently showed that an immune response against this antigen was increased in polyp patients and stage I/II CRC patients as compared to asymptomatic individuals. As a control, the humoral immune response to endotoxin was determined by the EndoCab assay from Hycult Biotechnology in the same study populations.
Endotoxin associated with loss of intestinal barrier function:
Endotoxin is an intrinsic component of the cell wall from the majority of Gram-negative intestinal bacteria and increased serum IgG levels against endotoxin have been associated with an impaired colonic barrier function. The latter analyses showed that anti-endotoxin IgG levels displayed a similar tendency as the anti-RpL7/L12 levels. However, in contrast to anti-RpL7/L12, the relative endotoxin antibody expression in patients with stage I/II tumors was markedly lower than in polyp patient. This suggests that increased anti-RpL7/L12 levels in early CRC patients cannot be fully attributed to a general loss of intestinal barrier function. Together, these findings are indicative for an increased exposure to antigen RpL7/L12 during early stages of colon carcinogenesis and may suggest that intestinal bacteria, such as S. gallolyticus, constitute a risk factor for the progression of pre-malignant 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 CRC.