TRANSIENT EXPOSURE TO CYTARABINE INCREASES PEPTIDE GROWTH-FACTOR RECEPTOR EXPRESSION AND TUMORIGENICITY OF MELANOMA-CELLS

We have demonstrated that anticancer drugs at cytostatic concentration s enhance the expression and function of epidermal growth factor (EGF- X) and transferrin (TRF-W) receptors on human tumor cells. We hypothes ized that these effects could represent a protective response of tumor cells to sublethal antiproliferative stimuli which could lead to enha nced growth potential 72 hours exposure of human melanoma GLL-19 cells to 1,000 nM ara-C induced growth inhibition and increased the number of EGF-R, TRF-R and nerve growth factor receptor (NGF-R) on cell surfa ce. Enhanced expression of beta(3) integrins CD49a, CD49c and CD49e, a (v) integrin CD51, beta(3) integrin CD61, CD58/LFA3 and collagen IV an d laminin was also detected in ara-C-treated GLL-19 cells. These chang es at the tumor cell surface were paralleled by increased in vitro adh esion, invasive potential and clonogenic growth in soft agar and in vi vo tumor formation. A more aggressive tumor cell phenotype is induced in human melanoma cells after transient exposure to cytostatic concent rations of ara-C.