Influence of increased c-Myc expression on the growth characteristics of human melanoma

Overexpression of the proto-oncogene c-myc has been associated with neoplas tic transformation in a variety of tumors. For human melanoma high c-myc ex pression has been found in the vertical growth phase and higher positivity reported in metastases than primary tumors. The principle aim of this study was to determine, whether c-Myc expression influences the metastatic behav ior of human melanoma in the absence of lymphocyte-mediated immune phenomen a. The growth characteristics and tumor biology of two c-myc transfectants of the human melanoma cell line IGR39D, expressing c-Myc 1.7 and three time s over baseline and the respective vector control were analyzed both in vit ro and in a severe combined immunodeficient mouse model in ville. Both c-my c transfectants showed increased growth rates, anchorage independent growth and directed cell movement in culture. Subcutaneously implanted IGR39D mel anomas highly overexpressing c-Myc spontaneously formed macroscopic metasta ses (lymph nodes and lung) in severe combined immunodeficient mice in all c ases (n = 7 per group), whereas less prominent c-Myc overexpression caused the development of only lung micrometastases. During the time period leadin g to terminal disease in animals injected with c-myc transfected human mela noma cells, melanoma development was not seen in vector controls. These fin dings suggest that constitutive high c-Myc expression in human melanoma res ults in a more aggressive growth behavior both in vitro and in vivo and fav ors metastasis in severe combined immunodeficient mice by factors unrelated to immune phenomena such as class I human leukocyte antigen downregulation known to be associated with c-Myc expression.