Identification of human melanoma cellular and secreted ligands for galectin-3.
The endogenous human tumor-associated galectin-3 (hL-31) is a functional molecule which acts as a receptor for ligands containing poly-N-acetyllactosamine sequences. However, little is known about its native ligand(s). In order to identify the ligand(s), the human melanoma cell line A375 was metabolically labeled with [3H]glucosamine, and total cell extracts and serum-free conditioned medium of the labeled cells were affinity-purified on immobilized recombinant hL-31 followed by elution with lactose, the specific sugar inhibitor of the lectin. Cellular ligands for hL-31 were found to be composed of the two lysosome-associated membrane proteins, LAMP-1 and LAMP-2, while secreted ligands consisted of two glycoproteins of 98 and 70 kDa. N-terminal protein microsequencing revealed that the 98 kDa and 70 kDa species share the same N-terminal sequence. The functional relevance of these secreted ligands was demonstrated by their ability to inhibit lectin-mediated hemagglutination in a manner similar to the specific sugar inhibitor lactose. Computer-assisted sequence library searches have identified the 98 kDa human melanoma secreted ligand to be the Mac-2-binding protein (Mac-2-BP), also known as the human lung tumor L3 antigen.
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Cancer Metastasis Program, Michigan Cancer Foundation, Detroit 48201.
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D000595:Amino Acid Sequence; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002240:Carbohydrate Sequence; D002352:Carrier Proteins / Q000378:metabolism; D037502:Galectin 3; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D008545:Melanoma / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D016326:Extracellular Matrix Proteins
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D037502:Galectin 3; D006023:Glycoproteins; D008024:Ligands; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins