IGF‐2 autocrine stimulation in tumorigenic clones of a human colon‐carcinoma cell line

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Abstract
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‐1 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‐1 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‐I 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. © 1995 Wiley‐Liss, Inc.