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

Int J Cancer. 1995 May 16;61(4):587-92. doi: 10.1002/ijc.2910610425.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / physiology
  • Clone Cells
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Culture Media, Serum-Free
  • Gene Amplification
  • Genes, myc
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis
  • Insulin-Like Growth Factor I / physiology
  • Insulin-Like Growth Factor II / biosynthesis
  • Insulin-Like Growth Factor II / physiology*
  • Stimulation, Chemical
  • Tumor Cells, Cultured


  • Culture Media, Serum-Free
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II