Effect of transfected interleukin-6 in non-tumorigenic and tumorigenic rat urothelial cell lines.
It has been suggested that interleukin (IL)-6 plays a significant role in bladder carcinomas. We conducted the present experiment to determine whether over-expressed IL-6 enhanced the tumorigenicity of a weakly tumorigenic rat bladder carcinoma, and whether it was sufficient to induce a tumorigenic phenotype in a non-tumorigenic, anchorage-dependent rat urothelial cell line, MYP3. P3M6-10 and P3M6-12 (anchorage-independent but non-tumorigenic) and MYP3T6 (anchorage-independent and tumorigenic) were isolated from MYP3 after treatment with MNU in vitro. None of these clones produced IL-6. The cells were transfected with an expression vector containing human IL-6 cDNA. The transfectants secreted a large amount of IL-6. In MYP3T6, over-expression of IL-6 enhanced tumorigenicity markedly in nude mice, as evidenced by acceleration of the growth rate in vivo as well as of anchorage-dependent and -independent growth. In P3M6-10 and P3M6-12, the introduced IL-6 cDNA markedly enhanced their growth potential, both on a plastic surface and in soft agar, but did not induce a tumorigenic potential. In MYP3, introduced IL-6 weakly enhanced their growth on a plastic surface, but caused neither tumorigenesis in nude mice nor colony formation in soft agar. Expression of gp130, an IL-6 signal transducer, was increased in IL-6-expressing clones, especially in the P3M6-10 and MYP3T6. We conclude that acquisition of the ability to synthesize endogenous IL-6 markedly accelerates the growth rate of weakly tumorigenic rat urothelial cells, but is not sufficient to induce a tumorigenic phenotype in non-tumorigenic cells.
Okamoto
M
M
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
Oyasu
R
R
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002455:Cell Division; D018014:Gene Transfer Techniques; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D051381:Rats; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
D015850:Interleukin-6