Glycosaminoglycans enhance human leukemic cell growth in vitro

We have previously shown that heparin and heparan sulfate stimulate the growth of human erythroleukemia cells in vitro in the presence of serum or plasma. To determine whether heparin and other glycosaminoglycans (GAGs) are involved in the growth of leukemia cells, effects of GAGs on the growth of three leukemia cell lines expressing different phenotypes, the HEL, HL60 and U937 cell lines were studied using both plasma clot and serum-free agar systems. The cells were cultured with different doses of six GAGs: hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin and heparan sulfate. It was found that, in serum-free agar system, no GAG was able to stimulate (HEL) cell growth. In contrast, when serum-containing culture systems were used, all six GAGs promoted colony formation of HL60 and U937 cells. In addition, all GAGs, except keratan sulfate, stimulated the growth of HEL cells. The findings suggest that the GAGs may play an indirect role in enhancing leukemia cell proliferation by different mechanisms.