PERLECAN IN HUMAN BONE-MARROW - A GROWTH-FACTOR-PRESENTING, BUT ANTIADHESIVE, EXTRACELLULAR-MATRIX COMPONENT FOR HEMATOPOIETIC-CELLS

Human perlecan is a heparan sulfate proteoglycan with a large core pro tein of 467 kDa to which three glycosaminoglycan side chains are attac hed. It belongs to the heparan sulfate proteoglycan family which has b een implicated in strong interactions between developing hematopoietic cells and their microenvironment in the bone marrow. Here we report t hat perlecan is highly expressed in the human bone marrow, as well as in long-term bone marrow cultures which are thought to mimic hematopoi esis in vitro. Expression of perlecan in this tissue was shown by Nort hern blotting of the 14-kb mRNA of the core protein and by immunofluor escence stainings. Functionally, perlecan shows a strong anti-adhesive effect on unfractionated bone marrow cells and on various hematopoiet ic cell lines, repelling the cells from the perlecan-coated area. In c ontrast, perlecan is adhesive for fibroblasts and endothelial cells. I t is suggested that the anti-adhesive site is located within the core protein of perlecan since heparitinase-treated perlecan still shows th e repellent effect. Although anti-adhesive for hematopoietic cells, pe rlecan is able to bind growth factors like granulocyte/macrophage-colo ny stimulating factor and present them to hematopoietic progenitor cel ls in a semi-solid colony assay. The functional role of a growth-facto r-binding extracellular matrix component in the bone marrow microenvir onment with anti-adhesive properties is uncertain but may be related t o compartmentalization.