A Mucoprotein with Colon‐Specific Determinants

Gold, David V.; Miller, Frederick W.

doi:10.1111/j.1399-0039.1978.tb01269.x

Cited by 15 publications

(3 citation statements)

References 21 publications

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“…This may explain the presence of autoantibodies to colonic tissue (24)(25)(26)(27) and immune complexes (28,29) observed by others in chronic ulcerative colitis. Recently, Gold and Miller (30) have shown that antisera from patients with this disease react with purified mucin antigens isolated from various segments of normal human intestine. The implication that circulating mucins and/or autoantibodies may exacerbate or perpetuate the pathophysiology of this disease, therefore, needs further investigation.…”

Section: Resultsmentioning

confidence: 99%

Radioimmunoassay of human intestinal goblet cell mucin. Investigation of mucus from different organs and species.

Qureshi¹,

Forstner²,

Forstner³

1979

J. Clin. Invest.

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A B S T R A C T We have developed a double-antibody radioimmulnoassay for the (quanititative imieassuremiienit of humiiani goblet cell mucin (GCM) in ordier to stu(ly intestinal imiutcus in human and other species. The assay used 3H-labeled mucin as the aintigen, rabbit antisera, and sheep anti-rabbit IgG aintiserat as the second antibody. A number of applications of the assay were investigated. A survey of human tissues revealed that Imlucinls of the rectumil, coloni, aind smiiall intestine had identical affinity for the rabbit antibody, whereas lung, eyelid conjunctiva, esophagus, and stomsach reacted less strongly. GCCM coineentrattion ranged from 1.9 to 14 ,ug mucin protein/ing tissue protein in the small and large intestinie, respectively. The radioiiiiinunioassay was also found to be useful as a imarker during the isolationi of GCM froIml huimlaIn ileal extracts, where it indicated that a 10,000-fold purification had l)een achieved. Antigenic determninants of the imiucin did not rely upon ABH blood grouip-specific terimiinal sugars in oligosaccharide chains. A comparison of imulcinis aimoing various species revealed a partial species specificity of the GCCM antiblody. Human GCXI cross-reacted writh dog, monkey, and rabbit mucins, l)ut not with imucins of rat, pig, toad, and oyster. Organ distribution of crossreactive imuticiins in rabbit tissues indicated a pLattern that was (qucalitatively similar to that seen in humiian tissues. Possible imlplications of these findings for auitoimin-une diseases are briefly discuissed.

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Section: Resultsmentioning

confidence: 99%

Radioimmunoassay of human intestinal goblet cell mucin. Investigation of mucus from different organs and species.

Qureshi¹,

Forstner²,

Forstner³

1979

J. Clin. Invest.

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“…The highest normal tissue reactivity is present in the colon with a sharp declination of reactivity in a cephalad direction. (31,32) Nongastrointestinal tissues are not reactive with this antiserum. Of importance, we had shown that the epitope structure was highly dependent upon the presence of the O-acetyl groups within the sialic acid.…”

Section: Discussionmentioning

confidence: 97%

Monoclonal Antibody G47 Engineered to be Reactive with Colorectal Tumor Mucin

Gold

2001

Hybridoma and Hybridomics

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We have previously shown that the normal adult colon produces a sialomucin containing the core trisaccharide 1,3 N-acetylgalactosamine. This structure was shown to be the epitope for a polyclonal antiserum that demonstrated colon "specific" activity. Antiserum binding is dependent upon the presence of O-acetylated sialic acids present at high concentrations in normal adult colon tissue. However, O-acetylation of sialic acids is decreased in colorectal cancer. Indeed, approximately 50% of colorectal carcinomas are nonreactive with this antiserum. In the current work, we used a de-O-acetylated, normal colon mucin as immunogen to generate monoclonal antibody (MAb) G47. Untreated normal colon mucins having a high O-acetylated sialic acid content were essentially nonreactive with G47. Removal of O-acetyl groups by saponification generated a reactive mucin derivative while subsequent treatment with neuraminidase abolished reactivity. By immunoperoxidase procedures MAb-G47 was reactive with approximately 85% of colorectal tumors while exhibiting relatively low reactivity with normal colon tissue. Mucins isolated from normal colon had on average less than 10% of the specific epitope as compared with mucins derived from colorectal tumors (p < 0.01). Initial immunohistochemical studies on tumors of noncolonic origin revealed few positive cases. The potential of MAb-G47 to assist in the diagnosis and/or prognosis of colorectal cancer is now being studied.

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“…Hence, this M3 antigen can be regarded as ectopic if present in gastric tumors. The presence of an antigen, normally restricted to the goblet cells of intestinal mucosa, is now well documented in colonic tumors (Goldenberg et al, 1976;Gold et Miller, 1978;Rapp et al, 1979;Mori et al, 1980;Ma et al, 1980) but no systematic investigations have been performed until now in gastric tumors, although the presence of an intestinal antigen has been reported by some authors (Kawasaki and Kimoto, 1974;Bara et al, 1978).…”

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confidence: 99%

Intestinal M3 antigen, A marker for the intestinal‐type differentiation of gastric carcinomas

Bara¹,

Hamelin²,

Martin³

et al. 1981

Intl Journal of Cancer

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The mucus-associated intestinal M3 antigen, normally restricted to intestinal goblet cells, was found in 35 out of 100 gastric adenocarcinomas belonging to intestinal (19/64) as well as diffuse (16/36) types according to Laurén's classification. often accompanying the other mucus-associated gastric M1 and M2 antigens. This M3 antigen was predominant over the gastric M antigens in 25 of these 35 tumors; 18 of these belonged to the histological intestinal type. According to the WHO classification, the M3 antigen was found to predominate in all mucinous adenocarcinomas (7/7), was never present in the undifferentiated carcinomas (0/8), but was also found in some tubulo-papillar (16/57) and signet-ring cell (12/27) adenocarcinomas. This antigen could be used as a new criterion and incorporated into a point system containing morphological and tumor cell behavioral considerations; then it would appear to be a good marker for intestinal-type differentiation. Indeed, 22 of these 25 gastric adenocarcinomas which produced predominantly M3 antigen showed such an intestinal-like differentiation. The M antigen pattern of gastric carcinoma suggested a duodenal rather than colonic-type differentiation.

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A Mucoprotein with Colon‐Specific Determinants

Cited by 15 publications

References 21 publications

Radioimmunoassay of human intestinal goblet cell mucin. Investigation of mucus from different organs and species.

Radioimmunoassay of human intestinal goblet cell mucin. Investigation of mucus from different organs and species.

Monoclonal Antibody G47 Engineered to be Reactive with Colorectal Tumor Mucin

Intestinal M3 antigen, A marker for the intestinal‐type differentiation of gastric carcinomas

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