Growth-factor-dependent migration of human lung-cancer cells

Abstract

Human lung tumors express different types of growth-factor receptors and corresponding ligands that might modulate several biological functions such as proliferation, differentiation, adhesion, and chemotaxis. In the present study, we have investigated the expression of different growth-factor receptors and their ligands in 5 established human lung-cancer cell lines. Using RT-PCR, we found that IGF-II/mannose-6-phosphate (M6P), c-met, EGF and c-kit receptors are expressed in 5/5 human lung-cancer cell lines. In order to investigate the biological function of these receptors, we performed Boyden-chamber assays using various growth factors as chemo-attractants. Human non-small-cell-lung-cancer cells (non-SCLC) migrated to recombinant human (rh)IGF I and IGF II at concentrations ranging from 1 to 1000 ng/ml, to HGF at 10 to 100 ng/ml, to EGF at 1 to 100 ng/ml and SCF at 1 to 50 ng/ml. In addition, we performed Boyden-chamber assays using U-1810-, U-1752- and Wart-derived serum-free conditioned medium as chemo-attractants. Serum-free conditioned medium stimulated migration of producer cells in a dose-dependent manner. The autocrine motility stimulating effect of U-1810-derived serum-free conditioned medium could be inhibited by 50% in the presence of neutralizing ahIGF-II antibodies in the assay, suggesting a possible autocrine motility loop in vitro.