Autor: P. De Baetselier, Anja B. Geldhof, Geert Raes, P Vandersteen, J. Van Ginderachter
Rok vydání: 1997
Předmět:
Zdroj: Clinical and Experimental Metastasis. 16:447-459
ISSN: 0262-0898
DOI: 10.1023/a:1006585525399
Popis: We have previously reported that transfection of mouse interferon gamma (IFN-gamma) in H-2Kk-positive BW variants (BW-Sp3) abolishes tumorigenicity and reduces metastatic capacity. To further increase the immunogenicity of BW-Sp3 cells, the gene for human interleukin 2 (huIL-2) was transfected in these cancer cells. Single BW-Sp3(huIL-2) and double BW-Sp3(huIL-2+IFN-gamma) transfectants were generated and their behavior was investigated as compared to parental and IFN-gamma-transfected BW-Sp3. Although expression of huIL-2 was equally effective as IFN-gamma in preventing tumor formation and reducing experimental metastasis, it did not confer protection to spontaneous metastases and even reversed the anti-metastatic activity of IFN-gamma. Inoculation of the BW variants in immunocompromised mice revealed that expression of IL-2 activates both T cells and aspecific immune effectors. However, in immunocompromised mice a clear pro-metastatic effect of IL-2 was recorded. Analysis of membrane antigens on the different variants showed a selective effect of huIL-2 on the expression of two surface antigens, i.e. L-selectin and metastatic T cell hybridoma antigen (MTH), which may contribute to metastasis. Hence upon expression of huIL-2 in T lymphoma variants, tumor outcome will depend on the balanced effects of the transfected cytokines on the immune response and the redirected effect on tumor progression.
Databáze: OpenAIRE
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