IGF-2 autocrine stimulation in tumorigenic clones of a human colon-carcinoma cell line.
Clonal analysis has shown that the SW613-S human colon-carcinoma cell line is heterogeneous: some cell clones display a high level of amplification of the c-myc gene and are tumorigenic in nude mice, whereas others have a small number of copies of this gene and are non-tumorigenic. Tumorigenic clones can proliferate in a chemically defined serum-free medium, whereas non-tumorigenic clones cannot. Suramin, like anti-insulin-like growth factor (IGF) or anti-IGF-I receptor antibodies, efficiently inhibits the growth of tumorigenic clones in defined medium. Inhibition by suramin or by anti-IGF antibodies can be reversed by pure IGF-I or IGF-2. Pure IGF-1 or IGF-2 or culture medium conditioned by tumorigenic clones can stimulate DNA synthesis in cells of non-tumorigenic clones. Co-culture with cells of tumorigenic clones sustains the growth of non-tumorigenic clones in defined medium. Cells of both tumorigenic and non-tumorigenic clones express high-affinity IGF-1 receptors at their surface but tumorigenic clones produce on average 5 times more IGF-1 and 25 times more IGF-2 than non-tumorigenic ones. These results indicate that autocrine growth stimulation of tumorigenic clones by IGFs through the IGF-1 receptor is essential for their ability to grow in defined medium. Since cells of tumorigenic clones produce IGF-2 at levels 80 times higher than IGF-1 and since an antibody strictly specific for IGF-1 has no effect on DNA synthesis in cells of tumorigenic clones grown in defined medium, IGF-2 is very likely the main effector in the autocrine loop.
Lamonerie
T
T
Laboratoire d'Oncologie Moléculaire, URA 1158 CNRS, Institut Gustave Roussy, Villejuif, France.
Lavialle
C
C
Haddada
H
H
Brison
O
O
D002455:Cell Division / Q000502:physiology; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016895:Culture Media, Serum-Free; D005784:Gene Amplification; D016259:Genes, myc; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000502:physiology*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II