Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL-2 cDNA.
The notion that tumour-cell-derived IL-2 might lead to paracrine stimulation of the host anti-tumour response was tested in a transplantable rat sarcoma model. Three HSNLV clones induced to secrete different amounts of human IL-2 following retroviral gene transfer showed reduced tumorigenicity and metastatic potential in athymic (nu/nu) and immunocompetent syngeneic rats which was directly related to the level of IL-2 secretion. In contrast, the tumorigenicity of HSNLV clones secreting a biologically inactive form of IL-2 (IL-2Lys20) was unaltered. T-lymphocyte-mediated rejection of ZipI, the highest IL-2 producer, was demonstrated histologically in hooded rats and infiltrating mononuclear cells were also observed in ZipI tumours growing in athymic rats. Tumours derived from IL-2-secreting HSNLV showed reduced or absent IL-2 secretion in immunocompetent rats, sometimes with associated loss of the IL-2 provirus, but continued to secrete IL-2 in nude rats. The host response to Moloney-helper-virus-infected HSNLV was also examined and the results represent a cautionary note to those undertaking experiments of a similar nature.
Russell
S J
SJ
Section of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, London, UK.
Eccles
S A
SA
Flemming
C L
CL
Johnson
C A
CA
Collins
M K
MK
D000818:Animals; D004247:DNA / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008979:Moloney murine leukemia virus / Q000235:genetics; D016297:Mutagenesis, Site-Directed; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010957:Plasmids; D051381:Rats; D011923:Rats, Nude; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D004247:DNA