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. 1999 Nov;81(5):822–831. doi: 10.1038/sj.bjc.6690770

The role of endogenous interleukin-2 in proliferation of human carcinoma cell lines

T E Reichert 3,2, Y Kashii 3, J Stanson 3, A Zeevi 1, T L Whiteside 1,2,3
PMCID: PMC2374306  PMID: 10555752

Abstract

Interleukin (IL-2) and IL-2Rβ/γ have been shown to be expressed in human carcinomas in culture and in situ. Recently, expression of endogenous IL-2 and IL-2R in the cytoplasm was found to be up-regulated in tumour cells undergoing mitosis. This observation suggested that similar to its role in lymphocytes, the IL-2/IL-R pathway is involved in the regulation of carcinoma cell proliferation. Metabolic labelling followed by immunoprecipitation and Western blot results showed that IL-2 in carcinomas was identical to that in human lymphocytes. However, tumour cells did not secrete IL-2 detectable by immunoassays, although membrane-associated IL-2 was detectable on a proportion of these cells cultured in the absence of exogenous IL-2. Antibodies to IL-2 failed to inhibit proliferation of carcinoma cells, but antibodies specific for the ligand-binding site of the IL-2R were growth inhibitory. Growth of tumour cells was also inhibited by the immunosuppressive drugs, cyclosporin A (CsA), FK506 and rapamycin (RPA), known to interfere with the IL-2 pathway in lymphocytes. To further confirm the role of endogenous IL-2 in the growth of carcinomas, tumour cells were incubated with an IL-2-specific antisense oligonucleotide. The treatment was shown to transiently inhibit IL-2 mRNA and IL-2 protein expression as well as proliferation of tumour cells. Tumour cells treated with IL-2-specific antisense oligonucleotide demonstrated increased apoptosis in comparison to untreated or sense oligonucleotide-treated control cells. The data indicate that in human carcinomas, endogenous IL-2 promotes growth and protects tumour cells from apoptosis. © 1999 Cancer Research Campaign

Keywords: IL-2, human carcinomas, tumour cell growth, IL-2/IL-2R pathway, antisense IL-2 oligonucleotides, apoptosis

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Selected References

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