Transient exposure to cytarabine increases peptide growth factor receptor expression and tumorigenicity of melanoma cells

We have demonstrated that anticancer drugs at cytostatic concentrations enhance the expression and function of epidermal growth factor (EGF-R) and transferrin (TRF-R) receptors on human tumor cells. We hypothesized that these effects could represent a protective response of tumor cells to sublethal antiproliferative stimuli which could lead to enhanced 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 surface. Enhanced expression of beta 3 integrins CD49a, CD49c and CD49e, av integrin CD51, beta 3 integrin CD61, CD58/LFA3 and collagen IV and laminin was also detected in ara-C-treated GLL-19 cells. These changes at the tumor cell surface were paralleled by increased in vitro adhesion, invasive potential and clonogenic growth in soft agar and in vivo tumor formation. A more aggressive tumor cell phenotype is induced in human melanoma cells after transient exposure to cytostatic concentrations of ara-C.