MODULATION OF CELL BEHAVIORS BY PROTEOGLYCANS WITH ANTI-CELL-SUBSTRATE ADHESION ACTIVITY-STUDIES ON INVOLVING MOLECULES AND THE MECHANISM

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Cell adhesion to substrate or cell is a crucial step that regulates a variety of sell behavior. We previously showed that PG-M, a large chondroitin sulfate proteoglycan had an jnhibitory activity for any types of cell-adhesion to ECM and proposed its general role in modulating sell-ECM interactions (J.Biol. Chem., 264, 8012, 1989) Several lines of evidence suggested that the activity could be due to the chondroitin sulfate chains immobilized onto ECM via the core protein moiety. To obtain the direct evidence for the role of PG-M, we investigated the effect of the anitisense specific inhibition of PG-M synthesis on the oncogenic adhesion of human osteosarcoma cells. The inhibition suppressed the malignant cell-adhesive phenotype, consistent with the idea that PG-M controls sell-ECM adhesion. To gain insight into the mechanism, we postulated that the chondroitin sulfate-induced inhibition of sell adhesion might be due to a sell surface receptor capable of intercing specifically with chondroitin sulfate chains, thereby influencing the clustering or conformational change of receptors for ECM molecules. The present results have indicated the occurrence of a 58-kDa protein which had an affinity to the PG-M- OR chondroitin sulfate-immobilized gel column. The interaction of the protein with the column required the presence of Ca^<2+>. According to these properties, 58-kDa protein is now designated glycocalfin could be extracted with a detergent-contergent-containing solution from the membrane fractions of cultured fibroblasts and from the homogenate of minced embryo bodirs. The amino asid sequences of purified of gycocolfin have shown that this molecule is a famiry of annexin VI.Further studies of the protein will answer the question whether our postulated mechanism for the anti-adhesion actibity of immobilized chondroitin sulfate chains could be operative or not.