TY - JOUR
T1 - Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL‐2 cDNA
AU - Russell, Stephen J.
AU - Eccles, Suzanne A.
AU - Flemming, Claudia L.
AU - Johnson, Caroline A.
AU - Collins, Mary K.L.
PY - 1991/1/21
Y1 - 1991/1/21
N2 - 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 tumorige‐nicity 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 Zip I, the highest IL‐2 producer, was demonstrated histologically in hooded rats and infiltrating mononuclear cells were also observed in Zip I 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.
AB - 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 tumorige‐nicity 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 Zip I, the highest IL‐2 producer, was demonstrated histologically in hooded rats and infiltrating mononuclear cells were also observed in Zip I 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.
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U2 - 10.1002/ijc.2910470213
DO - 10.1002/ijc.2910470213
M3 - Article
C2 - 1988368
AN - SCOPUS:0026026646
SN - 0020-7136
VL - 47
SP - 244
EP - 251
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -