Growth-factor-dependent migration of human lung-cancer cells.
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.
Department of Lung Medicine, Karolinska Institute at Huddinge University Hospital, Sweden. Cecilia.Bredin@impi.ki.se
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Bredin
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Liu
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Hauzenberger
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Klominek
D002465:Cell Movement; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000503:physiopathology*; D017978:Receptors, Growth Factor / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D017978:Receptors, Growth Factor