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 Ca2+-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.

Glycan-Dependent and -Independent Dual Recognition between DC-SIGN and Type II Serine Protease MSPL/TMPRSS13 in Colorectal Cancer Cells

“…Our findings strongly suggest the presence of tumor-associated Le glycans in human colon tumors. Indeed, we observed strong expression of MBP high-affinity ligands in 38.5% of human colorectal carcinoma tissues, but not in adjacent nonmalignant tissues where blood-type Le glycans were expressed [42]. Thus, it is possible that MSPL expressed in colon cancer cells harbors complicated tumor-associated Le glycans.…”

The Clinical Significance of DC-SIGN and DC-SIGNR, which Are Novel Markers Expressed in Human Colon Cancer

“…Nonaka reported that Mac-2BP, a protein expressed on some colon carcinoma cells, could be recognized by DC-SIGN through Le glycans [26] . Recently this group also found that tumor-associated Lewis glycans displayed affinity for another C-type serum lectin, mannan-binding protein, with fructose being involved in this interaction rather than mannose [40] . Therefore the interaction between DC-SIGN and colon cancer cells may not simply be one-for-one, which is an idea that is consistent with our experimental data.…”

Myeloid C-type lectin receptors in skin/mucoepithelial diseases and tumors

“…Serum levels of soluble DC‐SIGN are reduced in colon cancer patients, and high serum levels of soluble DC‐SIGN correlate with long‐term survival, suggesting that this molecule could serve as a novel prognostic biomarker . MICL is detected on acute myeloid leukemia CD34 + stem cells, and mAbs against this molecule cause Ab‐dependent cellular cytotoxicity against both cultured and freshly isolated leukemia cells, suggesting a new therapeutic strategy against acute leukemia …”