Mannan-Binding Protein, a C-Type Serum Lectin, Recognizes Primary Colorectal Carcinomas through Tumor-Associated Lewis Glycans

Abstract

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.