Interleukin-6 stimulates clonogenic growth of primary and metastatic human colon carcinoma cells.
Interleukin-6 (IL-6) is a pleiotropic cytokine which exerts biological activities on various cell types including neoplastic cells. We have investigated the biological effect of IL-6 and the expression of IL-6 receptors (IL-6R) on human colorectal carcinoma cell lines. Isreco-1 was derived from the primary site of a colon cancer while Isreco-2 and Isreco-3 were established from a liver and peritoneal metastasis of the same patient. IL-6 stimulated colony formation in methylcellulose of Isreco-1 cells to 150% (P < 0.05). The effect was even more pronounced on the metastatic Isreco-2 line where colony numbers in the presence of IL-6 were enhanced up to four-fold (P < 0.0001) in a dose-dependent fashion. An anti-IL-6 antibody completely abolished this growth stimulatory effect of IL-6. RT-PCR analysis revealed transcripts for IL-6Ralpha and gp 130 in these cell lines. Experiments with additional cell lines confirmed the general expression of gp130 but showed limited expression of the IL-6Ralpha chain. Surprisingly, about half of the cell lines tested expressed IL-6 mRNA at low levels which was not translated into protein. Our results suggest that IL-6 can potently stimulate anchorage-independent growth of some colorectal carcinoma cells. This stimulation appears to occur through a paracrine mechanism.
Schneider
M R
MR
Institute of Molecular Animal Breeding, Gene Center, Munich, Germany.
Hoeflich
A
A
Fischer
J R
JR
Wolf
E
E
Sordat
B
B
Lahm
H
H
D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary; D009362:Neoplasm Metastasis; D010534:Peritoneal Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins