Enhanced invasion and liver colonization by lung carcinoma cells overexpressing the type 1 insulin-like growth factor...

The receptor for the type 1 insulin-like growth factor (IGF-1R) and its ligands IGF-1 and IGF-2 play important roles in the maintenance of the malignant phenotype. In previous studies with two sublines of the Lewis lung carcinoma (H-59 and M-27, expressing high and low levels of IGF-1R, respectively) we have shown that receptor levels in these tumor cells correlated with metastasis to the liver. In the present study we asked whether the metastatic properties can be modulated by increasing receptor levels. M-27 carcinoma cells were transfected with a plasmid vector expressing a full-length human IGF-1R cDNA. Expression of the human receptor in the stable transfectants was confirmed by RT-PCR and immunoprecipitation analysis. These cells had an enhanced proliferative response to IGF-1 and hepatocyte-conditioned medium and an increased clonogenic potential in semisolid medium. Moreover, they acquired an invasive potential as measured in the reconstituted basement membrane (Matrigel) invasion assay. When inoculated via the splenic/portal route in vivo, these cells but not mock-transfected cells gave rise to multiple tumor nodules. The results suggest that IGF-1R can modulate several cellular functions which impact on the metastatic phenotype including invasion and liver colonization.