The role of individual eicosanoids of the arachidonic acid (AA) cascade in the growth control of A549 human lung adenocarcinoma cells has been studied. Cyclooxygenase and lipoxygenase metabolites of [14C]AA incorporated were actively synthesized in the cultures of tumor cells with full confluence unaccomplished. In such cultures inhibitors of AA metabolism (indomethacin and esculetin) and also a lipoxygenase metabolite of AA, 15-hydroxyeicosatetraenoic acid (15-HETE), significantly suppressed the incorporation of [3H]thymidine and biosynthesis of prostaglandin E2 (PGE2). Other lipoxygenase metabolites of AA (5-HETE and 12-HETE) had no effect on these parameters. The basic fibroblast growth factor (bFGF) had practically no affect on the growth of A549 cells and the PGE2 production in cultures with 5% fetal calf serum (FCS); however, in the presence of 0.5% FCS this factor significantly increased the number of tumor cells. The growth-stimulating effect of bFGF was completely abolished by a cyclooxygenase inhibitor indomethacin. The data suggest a key role of PGE2 in the growth control of A549 cells with an active synthesis of cyclooxygenase and lipoxygenase metabolites of AA, its importance in realization of the mitogenic effect of bFGF, and specific features of 15-HETE as a down-regulator of the PGE2-dependent proliferation.

Inhibitory effect of glycosaminoglyeans isolated from peripheral blood granulocytes of patients with chronic myeloleukemia and normal subjects on increment in colony-forming units of fibroblasts in monolayer cultures of rat bone marrow is determined by the degree of sulfation of their main component ehondroitin-4-sulfate and by increased content of heparan sulfate. Key Words: glycosaminoglycans; increase in the number of colony-forming units of bone marrow fibroblastsGlycosaminoglycans (GAG) and their conjugates with proteins proteoglycans are the major components of the extracellular matrix of bone marrow. Human bone marrow stromal cells produce ehondroitin-6-sulfate (C-6-S), dermatan sulfate, and heparan sulfate that participate in cell-to-cell reactions with stem cells and hemopoiesis precursor cells, determining their adhesion, migration, proliferation, and differentiation [4,6]. On the other hand, bone marrow and blood hemopoietic cells contain GAG in the form of proteoglycans and free polysaccharide chains. The major component of granuloeytic GAG is polydispersed C-4-S, while heparan and dermatane sulfates are minor components [5]. Activation of hemopoietic cells is associated with intense production and secretion of GAG functioning as mediators, reacting with bone marrow stromal elements [4,5]. However, the mediator role of hemopoietie cell GAGs has not been evaluated. We revealed the ability of GAG isolated from human blood granuloeytes to modify pro- MATERIALS AND METHODSExperiments were carried out in rat bone marrow monolayer cultures [2]. Bone marrow cells were isolated from femoral bone of Wistar rats weighing 200-250 g. The cells (0.5-5.0x 106) were expanded in Carrel's flasks (25 cm 2) in RPMI-1640 (Sigma) with 15% fetal calf serum in an atmosphere with 5% CO,. Nonadherent bone marrow cells were removed after 48 h, then GAG in a concentration of 1-5 I~g uronic acids/ml and chondroitin sulfates (0.5, 1, 10, and 30 ps/ml) were added. Two fractions of low-and sulfated GAGs were used They were isolated by the papain method [3] from acetone-dried blood granulocytes from patients with CML during the chronic 0007-4888/98/0003-0282520.00 elgg8 Plenum .Publishing Corporation

No abstract

No abstract

No abstract