title: Lactose-functionalized dendrimers arbitrate the interaction of galectin-3/MUC1 mediated cancer cellular aggregation.
abstract: By using lactose-functionalized poly(amidoamine) dendrimers as a tunable multivalent platform, we studied cancer cell aggregation in three different cell lines (A549, DU-145, and HT-1080) with galectin-3. We found that small lactose-functionalized G(2)-dendrimer 1 inhibited galectin-3-induced aggregation of the cancer cells. In contrast, dendrimer 4 (a larger, generation 6 dendrimer with 100 carbohydrate end groups) caused cancer cells to aggregate through a galectin-3 pathway. This study indicates that inhibition of cellular aggregation occurred because 1 provided competitive binding sites for galectin-3 (compared to its putative cancer cell ligand, TF-antigen on MUC1). Dendrimer 4, in contrast, provided an excess of ligands for galectin-3 binding; this caused crosslinking and aggregation of cells to be increased.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, 103 Chemistry and Biochemistry, Bozeman, MT 59717 (USA).
authors.forename: Anna K
authors.initials: AK
authors.lastname: Michel
authors.forename: Pratima
authors.initials: P
authors.lastname: Nangia-Makker
authors.forename: Avraham
authors.initials: A
authors.lastname: Raz
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Cloninger
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D007785:Lactose / Q000031:analogs & derivatives / Q000378:metabolism*; D018396:Mucin-1 / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D050091:Dendrimers; D037502:Galectin 3; D018396:Mucin-1; C104700:PAMAM Starburst; C016467:Thomsen-Friedenreich antigen; D007785:Lactose
keywords: aggregation; cancer; galectin-3; lactose-functionalized dendrimers; mucin 1