Undersulfation of glycosaminoglycans reduces the proliferation of a leukemia cell line in vitro.
Leukemia represents the clonal expansion of an individual cell lineage of the hematopoietic system at a specific point of its maturation and development. This dysregulated expansion of cells is often accompanied by altered adherence to the bone marrow microenvironment and abnormalities in endogenous cytokine production by neoplastic cells. Proteoglycans (PGs) synthesized by neoplastic cells may interact with extracellular matrix (ECM) molecules and/or locally produced cytokines. It is believed that these events may be mediated by the glycosaminoglycan (GAG) moiety of PGs such as heparan or chondroitin sulfate, and depends on its charge. The strength of GAG-cytokine binding may be determined by the extent of sulfation of the GAG chains. The synthesis, metabolism and biological role of PGs in hematopoietic malignancies have not been clearly defined. In order to study how alterations of GAGs in leukemic cells may alter cellular behavior, we treated the murine myeloid leukemic cell line WeHi-3B with sodium chlorate. This drug reduces the sulfation of GAGs, since chlorate is a potent inhibitor of sulfate adenylyltransferase. The undersulfated GAGs produced by WeHi-3B cells were not efficient in controlling the mitotic rate of the cells, since a decrease in cell proliferation was observed in vitro. These data suggest that the complexes formed by GAGs with ECM components and/or cytokines may have an important role in the induction of leukemic cell proliferation. It is possible that the stimulatory activity elicited by this binding may be dependent upon the organization of these complexes.
Alvarez-Silva
M
M
Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Catarina, Florianopolis, Brasil.
Trentin
A G
AG
D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D007942:Leukemia, Experimental / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006025:Glycosaminoglycans; D011509:Proteoglycans; D013431:Sulfates