Mannan-binding protein, a C-type serum lectin, recognizes primary colorectal carcinomas through tumor-associated Lewis glycans

Mannan (mannose)-binding protein (MBP) is a C-type serum lectin that plays a key role in innate immunity. MBP forms large multimers (200-600 kDa) and exhibits broad specificity for mannose, N-acetylglucosamine, and fucose. MBP exhibits high affinity for unique oligosaccharides that have been isolate...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2014-02, Vol.192 (3), p.1294-1301
Main Authors: Nonaka, Motohiro, Imaeda, Hirotsugu, Matsumoto, Shogo, Yong Ma, Bruce, Kawasaki, Nobuko, Mekata, Eiji, Andoh, Akira, Saito, Yasuharu, Tani, Tohru, Fujiyama, Yoshihide, Kawasaki, Toshisuke
Format: Article
Language:English
Subjects:
Adenocarcinoma - chemistry
Adenocarcinoma - diagnosis
Adenocarcinoma - mortality
Adenocarcinoma, Mucinous - chemistry
Adenocarcinoma, Mucinous - diagnosis
Adenocarcinoma, Mucinous - mortality
Adult
Aged
Aged, 80 and over
Antigens, Neoplasm - analysis
CA-19-9 Antigen - analysis
Colorectal Neoplasms - chemistry
Colorectal Neoplasms - diagnosis
Colorectal Neoplasms - mortality
Epithelium - chemistry
Fluorescent Antibody Technique, Indirect
HLA-DR Antigens - analysis
Humans
Intestinal Mucosa - chemistry
Ligands
Lymphocytes, Tumor-Infiltrating - chemistry
Mannose-Binding Lectin - physiology
Middle Aged
Neoplasm Metastasis
Oligosaccharides - analysis
Predictive Value of Tests
Proportional Hazards Models
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Summary:Mannan (mannose)-binding protein (MBP) is a C-type serum lectin that plays a key role in innate immunity. MBP forms large multimers (200-600 kDa) and exhibits broad specificity for mannose, N-acetylglucosamine, and fucose. MBP exhibits high affinity for unique oligosaccharides that have been isolated from human colorectal carcinoma (SW1116) cells and characterized as highly fucosylated high m.w. type 1 Lewis glycans. In this study, we first demonstrated that MBP recognizes human primary colorectal carcinoma tissues through tumor-associated MBP ligands. We performed fluorescence-based histochemistry of MBP in human colorectal carcinoma tissues and showed that MBP clearly stained cancer mucosae in a Ca(2+)-dependent manner. Coincubation with plant (Aleuria aurantia) lectin, but not Con A, blocked MBP staining, indicating that fucose, rather than mannose, is involved in this interaction. The expression of MBP ligands was detected in 127 of 330 patients (38.5%), whereas, most significantly, there was no expression in 69 nonmalignant tissues. The MBP-staining pattern in cancer mucosae significantly overlapped with that of Lewis b [Fucα1-2Galβ1-3(Fucα1-4)GlcNAc] staining, but the Lewis b staining in normal tissues was not associated with MBP staining. In addition, the MBP staining correlated inversely with the expression of CA19-9 Ag, and MBP stained 11 of 25 (44%) CA19-9 (sialyl Lewis a [NeuAc(α2-3)Galβ1-3(Fucα1-4)GlcNAc])(-) colorectal carcinoma tissues. We found a favorable prognosis in patients with MBP ligand(+) tumors. These results suggest that selective recognition of cancer cells by endogenous MBP seems to be associated with an antitumor effect and that tissue staining with MBP in combination with CA19-9 may serve as a novel indicator of colorectal carcinoma tissues.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1203023