INHIBITION OF K1735-M2 MELANOMA CELL INVASION IN-VITRO BY RETINOIC ACID

Melanoma cell invasion in vitro was tested by means of confrontation c ultures of melanoma multicellular spheroids with rounded fragments of embryonic chick heart tissue. Quantitative determination of invasion w as performed using a computerized image analysis program, facilitating the evaluation of the efficacy of potentially anti-invasive compounds . Retinoic acid (RA; 1 mum) considerably impaired K1735-M2 melanoma ce ll invasion, as demonstrated by various measuring parameters. Paramete r TUMAREA, expressing the amount of tumor tissue, indicates a growth i nhibitory effect and the invasion parameter STRCSTR shows that after t reatment with RA the stromal component was better preserved than in un treated controls. Besides the inhibitory effect of RA on melanoma cell invasion in confrontation cultures, RA increased the dynamics of adhe sion of melanoma cells to the extracellular matrix components type I c ollagen and laminin, and slightly impaired melanoma cell directional m igration. Fluorescence microscopy using rhodamine-labeled phalloidin s howed that RA also modulated the organization of the actin cytoskeleto n by inducing the formation of actin-containing stress fibers. Our dat a show that 1 muM RA exhibited a pronounced anti-invasive effect on hi ghly metastatic melanoma cells in vitro. Impairment of host tissue deg radation, altered adhesion abilities, changes in the actin cytoskeleto n, as well as the antiproliferative effect may all account for inhibit ion of melanoma cell invasion.