The
tumor-associated
antigen 90K (TAA90K)/Mac-2-
binding protein implicated in
cancer progression and
metastasis is modified by beta1-6 branched N-linked
oligosaccharides in
colon cancer cells,
glycans shown to contribute to
cancer metastasis. To elucidate the role of TAA90K in
colon cancer, we examined its expression and function in human colon
tumors and colon
carcinoma cell lines. Immunohistochemical analyses of colon
tumors revealed elevated expression of TAA90K in all samples analyzed compared to normal colon. To examine the function of TAA90K in
colon cancer, we carried out
protein and cell binding assays using TAA90K-His purified from HT-29 cells colon
carcinoma cells infected with recombinant vaccinia virus expressing TAA90K containing a C-terminal
poly-histidine tag. TAA90K-His bound to
fibronectin,
collagen IV, laminins-1, -5, and -10 and
galectin-3 (Mac-2) but poorly to
collagen I and
galectin-1. As expected, binding of TAA90K to
galectin-3 was dependent on
carbohydrate since it was inhibitable by
lactose and asiolofetuin, and a TAA90K-His glycoform purified from HT-29 cells treated with the glycosylation inhibitor
1-deoxymannojirimycin bound poorly to
galectin-3. Unlike TAA90K isolated from other cell types, TAA90K-His isolated from
colon cancer cells failed to mediate adhesion of
colon cancer and normal cell lines, possibly due to cell-type specific glycosylation of TAA90K-His and/or its putative cellular receptor. However, at low concentrations, TAA90K-His enhanced galectin-3-mediated HT-29 cell adhesion while at high concentrations, it inhibited cell adhesion. Thus, a possible mechanism by which TAA90K may contribute to
colon cancer progression is by modulating
tumor cell adhesion to extracellular
proteins, including
galectin-3.