The role of galactose, lactose, and galactose valency in the biorecognition of N-(2-hydroxypropyl)methacrylamide copolymers by human colon adenocarcinoma cells.
OBJECTIVE
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.
David
Ayelet
A
The Hebrew University of Jerusalem, Faculty of Medicine, School of Pharmacy, Israel.
Kopecková
Pavla
P
Kopecek
Jindrich
J
Rubinstein
Abraham
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005690:Galactose / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007785:Lactose / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D008689:Methacrylates; D007785:Lactose; C032802:hydroxypropyl methacrylate; D005690:Galactose