PURPOSE: To examine the beta-galactoside and beta-lactoside binding capacity of three human colon-adenocarcinoma cell lines and their sugar specificity, using N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of galactosamine, lactose, and triantennary galactose. METHODS: Three types of HPMA copolymers containing the saccharide epitopes galactosamine (P-Gal), lactose (P-Lac), or triantennary galactose (P-TriGal) were synthesized. The relationship between the content of the saccharide moieties, the valency of the galactose residues, and their biorecognition by the cell lines (Colo-205, SW-480, and SW-620) was investigated using flow cytometry and confocal fluorescence microscopy analysis. RESULTS: The binding of the glycoconjugates to the human colonadenocarcinoma cell lines was dependent on the type and the number of bound sugar residues per macromolecule. The higher the sugar contents in the HPMA copolymers, the higher the extent of binding. Although introduction of galactoside residues into the HPMA copolymer resulted in a significant increase in the binding of the copolymers to the cells, low biorecognition of the lactoside-containing HPMA copolymers by all cell lines used was observed. The trivalent galactoside-containing HPMA copolymers did not yield a notable glycoside cluster effect for the beta-galactoside-binding lectin expressed on human colon-adenocarcinoma cells. Among the various cell line little differences in the extent of binding of the glycopolymers to the cells were observed. The data on the internalization of HPMA copolymer conjugates obtained by confocal fluorescence microscopy correlated well with the flow cytometry analysis of their biorecognition by target cells. CONCLUSIONS: The lectin-mediated endocytosis of the HPMA glycoconjugates in human colon cancer cell lines suggests their potential use as targeting tools of cytotoxic drugs to colon adenocarcinoma.
PURPOSE: To examine the beta-galactoside and beta-lactoside binding capacity of three humancolon-adenocarcinoma cell lines and their sugar specificity, using N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates of galactosamine, lactose, and triantennary galactose. METHODS: Three types of HPMA copolymers containing the saccharide epitopes galactosamine (P-Gal), lactose (P-Lac), or triantennary galactose (P-TriGal) were synthesized. The relationship between the content of the saccharide moieties, the valency of the galactose residues, and their biorecognition by the cell lines (Colo-205, SW-480, and SW-620) was investigated using flow cytometry and confocal fluorescence microscopy analysis. RESULTS: The binding of the glycoconjugates to the human colonadenocarcinoma cell lines was dependent on the type and the number of bound sugar residues per macromolecule. The higher the sugar contents in the HPMA copolymers, the higher the extent of binding. Although introduction of galactoside residues into the HPMA copolymer resulted in a significant increase in the binding of the copolymers to the cells, low biorecognition of the lactoside-containing HPMA copolymers by all cell lines used was observed. The trivalent galactoside-containing HPMA copolymers did not yield a notable glycoside cluster effect for the beta-galactoside-binding lectin expressed on humancolon-adenocarcinoma cells. Among the various cell line little differences in the extent of binding of the glycopolymers to the cells were observed. The data on the internalization of HPMA copolymer conjugates obtained by confocal fluorescence microscopy correlated well with the flow cytometry analysis of their biorecognition by target cells. CONCLUSIONS: The lectin-mediated endocytosis of the HPMA glycoconjugates in humancolon cancer cell lines suggests their potential use as targeting tools of cytotoxic drugs to colon adenocarcinoma.
Authors: P J Julyan; L W Seymour; D R Ferry; S Daryani; C M Boivin; J Doran; M David; D Anderson; C Christodoulou; A M Young; S Hesslewood; D J Kerr Journal: J Control Release Date: 1999-02-22 Impact factor: 9.776
Authors: T Irimura; Y Matsushita; R C Sutton; D Carralero; D W Ohannesian; K R Cleary; D M Ota; G L Nicolson; R Lotan Journal: Cancer Res Date: 1991-01-01 Impact factor: 12.701
Authors: P A Vasey; S B Kaye; R Morrison; C Twelves; P Wilson; R Duncan; A H Thomson; L S Murray; T E Hilditch; T Murray; S Burtles; D Fraier; E Frigerio; J Cassidy Journal: Clin Cancer Res Date: 1999-01 Impact factor: 12.531