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Abstract

We have immunohistochemically examined the distribution of the H antigens of type 1, type 2 and type 3/4 chains of the ABO(H) histo-blood group system in human normal colon and in colon cancer using three monoclonal antibodies specific for each of the H type 1/2, H type 2, and the H type 3/4 chain. We unexpectedly found that mucosa of the normal colon from secretors but not that from nonsecretors expressed only H type 1 and did not express H type 2 or H type 3/4. The H type 1 was expressed in goblet cells. Positive goblet cells expressing H type 1 were decreased in number progressively from the proximal colon to the rectum. In tumors, 4 (57%) of 7 cancer tissues of the proximal colon from secretors expressed no H type 1, whereas all 8 cancer tissues of the distal colon from secretors expressed H type 1. The aberrant expressions of H type 2 and H type 3/4 (47 and 67%, respectively) were found in cancer tissues from both the proximal and the distal colon. Tumors from nonsecretors did not express any H antigens. Our results suggested that the expression of H type 1 in the normal colon and the aberrant expressions of H type 2 and H type 3/4 in colon cancer tissues were regulated by FUT2-encoded Se type alpha(1,2)fucosyltransferase. However, UEA-I-positive substance(s) rather than H type 2 were uniquely expressed throughout the normal colon and in colon cancers from both secretors and nonsecretors.

Colorectal cancer cell lines show striking diversity of their O-glycome reflecting the cellular differentiation phenotype

“…We have also observed that blood group antigen H types 2 and 3 were more abundant than H type 1 antigen in CRC cell lines. Similarly, antibody staining studies showed region-specific expression of mainly H type 1 blood group antigen H in healthy colon tissue, in contrast to colon cancer tissues aberrantly expressing blood group antigens H type 2 and 3 associated with tumour progression in the distal colon and rectum [36].…”

“…Apart from the erythrocytes, the ABH antigens can be expressed also in the gastrointestinal tract and secretions, where the Se-FUT enzyme (FUT2) is responsible for their biosynthesis [35]. However, several reports have demonstrated the expression of blood group ABH antigens in colon cancers from non-secretors with inactive enzyme [36,37]. Cell lines showing expression of blood group H antigens such as CaCo-2, HCT15, HCT8, SW948, SW1116, and SW837 were derived from tumours of blood group O secretor positive individuals [38].…”

Association between the ABO blood group and the human intestinal microbiota composition

“…In this study, we hypothesized that the ABO blood group antigens, which are expressed on the intestinal mucosa of secretor individuals [16,17] determine the gastrointestinal microbiota composition in healthy individuals. We recruited 79 healthy adult volunteers living in Southern Finland to test this hypothesis.…”

“…Krusius et al reported that ABO blood group antigens are present on erythrocyte glycoproteins as polyglycosyl chains [24]. Studies focusing on the expression of glycans in the human intestine have identified the presence of ABO type 1 glycans in the mucosal layer covering human orogastrointestinal tract and have shown that the fucosylated glycans, including ABO blood group glycan antigens, are detected less abundantly towards the distal parts of the intestine [16,17]. The ABO blood group glycans are reported to be exported to the mucus layer from goblet cells residing in the crypts of the small intestine [17].…”

Structural diversity and biological importance of ABO, H, Lewis and secretor histo-blood group carbohydrates

“…It has been demonstrated that the expression of H type 1 carbohydrates in the normal colon is under the control of FUT2 gene-encoded fucosyltransferase. However the aberrant expressions of H type 2 and H type 3/4 carbohydrates in colon cancer tissues of secretors is regulated by the same enzyme 57 . The reasons underlying these changes have not been clarified.…”