LAMINARIN SULFATE MIMICS THE EFFECTS OF HEPARIN ON SMOOTH-MUSCLE CELL-PROLIFERATION AND BASIC FIBROBLAST GROWTH FACTOR-RECEPTOR BINDING ANDMITOGENIC ACTIVITY

Heparin and heparin-like molecules may function, apart from their effe ct on hemostasis, as regulators of cell growth and neovascularization. We investigated whether similar effects are exerted by laminarin sulf ate, an unrelated polysulfated saccharide isolated from the cell wall of seaweed and composed of chemically O-sulfated beta-(1,3)-linked glu cose residues. Laminarin sulfate exhibits about 30% of the anticoagula nt activity of heparin and is effective therapeutically in the prevent ion and treatment of cerebrovascular diseases. We characterized the ef fect of laminarin sulfate on interaction of the heparin-binding angiog enic factor, basic fibroblast growth factor (bFGF), with a naturally p roduced subendothelial extracellular matrix (ECM) and with cell surfac e receptor sites. Laminarin sulfate (1-2 mu g/ml) inhibited the bindin g of bFGF to ECM and to the surface of vascular smooth muscle cells (S MC) in a manner similar to that observed with heparin. Likewise, lamin arin sulfate efficiently displaced both ECM- and cell-bound bFGF at co ncentrations as low as 1 mu g/ml. Both laminarin sulfate and heparin e fficiently induced restoration of bFGF receptor binding in xylosyltran sferase-deficient CHO cell mutants defective in initiation of glycosam inoglycan synthesis. Moreover, laminarin sulfate elicited bFGF recepto r activation and mitogenic response in heparan sulfate (HS)-deficient, cytokine-dependent lymphoid cells. These results indicate that lamina rin sulfate effectively replaced the need for heparin and HS in the in duction of bFGF receptor binding and signaling. In other experiments, laminarin sulfate was found to inhibit the proliferation of vascular S MC in a manner similar to that observed with heparin. These effects of laminarin sulfate may have potential clinical applications in diverse situations such as wound healing, angiogenesis, and atherosclerosis. (C) 1995 Wiley-Liss, Inc.