ENHANCED INVASION AND LIVER COLONIZATION BY LUNG-CARCINOMA CELLS OVEREXPRESSING THE TYPE-1 INSULIN-LIKE-GROWTH-FACTOR RECEPTOR

The receptor for the type 1 insulin-like growth factor (IGF-1R) and it s ligands IGF-1 and IGF-2 play important roles in tile maintenance of tile malignant phenotype. In previous studies with two sublines of the Lewis lung carcinoma (H-59 and M-27, expressing high and low levels o f IGF-1R, respectively) we have shown that receptor levels in these tu mor cells correlated with metastasis to the liver. In the present stud y we asked whether the metastatic properties can be modulated by incre asing receptor Levels, M-27 carcinoma cells were transfected with a pl asmid vector expressing a full-length human IGF-1R cDNA, Expression of the human receptor iu the stable transfectants was confirmed by RT-PC R and immunoprecipitation analysis. These cells had all enhanced proli ferative response to IGF-1 and hepatocyte-conditioned medium and an in creased clonogenic potential in semisolid medium. Moreover, they acqui red an invasive potential as measured in the reconstituted basement me mbrane (Matrigel) invasion assay. When inoculated via the splenic/port al route in vivo, these cells but not mock-transfected cells gave rise to multiple tumor nodules. The results suggest that IGF-1R can modula te several cellular functions which impact on the metastatic phenotype including invasion and liver colonization. (C) 1998 Academic Press.