THE PROTEOGLYCAN PERLECAN IS EXPRESSED IN THE ERYTHROLEUKEMIA CELL-LINE K562 AND IS UP-REGULATED BY SODIUM-BUTYRATE AND PHORBOL ESTER

Perlecan is a modular heparan sulfate proteoglycan that harbors five d omains with homology to the low density lipoprotein receptor, epiderma l growth factor, laminin and neural cell adhesion molecule. Using a mo noclonal antibody directed against the laminin-like domain of perlecan , we have recently shown that perlecan is widely expressed in all lymp horeticular systems. To investigate further this observation we have s tudied the expression of perlecan in two human leukemic cell lines. Us ing reverse transcriptase-PCR, ribonuclease protection assay, and meta bolic labeling we detected significant perlecan expression in the mult ipotefitial cell line K562, originally derived from a patient with chr onic myelogenous leukemia. In contrast, the promyelocytic cell line HL -60 expressed perlecan at barely detectable levels. These results were intriguing because the K562 cells do not assemble or produce a classi cal basement membrane. Following induction with either sodium butyrate or the phorbol diester 12-O-tetradecanoylphorbol-13-acetate (TPA), K5 62 and HL-60 differentiate into early progenitor cells with erythroid or megakaryocytic properties, respectively. Following treatment of K56 2 and HL-60 cells with either of these agents, perlecan expression was markedly increased in K562 cells. In contrast, we could detect perlec an protein synthesis in HL-60 cells only at very low levels, even afte r induction with TPA or sodium butyrate. Collectively, these results i ndicate that perlecan is actively synthesized by bone marrow derived c ells and suggest that this proteoglycan may play a role in hematopoiet ic cell differentiation.