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Summary.We have evaluated the effects of all-trans-retinoic acid (RA) on the adhesion of the human promyelocytic cell line NB4 to various components of the extracellular matrix. NB4 cells, radiolabelled with 111 Indium, showed a 2-3-fold increase (P < 0·001) in adhesion to fibronectin and thrombospondin upon RA (3 × 10 ¹7 M) treatment, whereas adhesion to collagen I, laminin and vitronectin was not modified. The increase in cell adhesion, observed as early as day 1, preceded cell differentiation and was concomitant with tyrosine phosphorylation events. Using flow cytometry, we analysed the expression of major receptors for fibronectin (a4b1 and a5b1) and for thrombospondin (avb3, aIIbb3, CD36 and CD47) on NB4 cells before and after RA treatment. Except for aIIbb3, which was induced on RA-treated cells, we found no significant increase in the expression of the other receptors, and a decrease in the expression of CD36, upon RA treatment. Preincubation of RA-treated cells with blocking antibodies demonstrated a role for a4b1 and a5b1 in cell adhesion to fibronectin and a5b1, aIIbb3, CD36 and CD47 in cell adhesion to thrombospondin. Experiments with the synthetic peptides GRGDS (0·2 mM) and CSVTCG (0·2 mM) confirmed the participation of integrins, and integrins and CD36, in adhesion of RA-treated cells to fibronectin and thrombospondin, respectively. Further inhibition by heparin (10 mg/ml) and/or recombinant heparin-binding domain of thrombospondin (TSP18) indicated the additional participation of heparin-like receptors in cell adhesion to thrombospondin. Our results indicate that increase in NB4 cell adhesion to fibronectin and thrombospondin upon RA treatment is likely to occur through a modulation of the functional state of several receptors for these proteins.

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