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Decreased tumorigenicity of a transplantable rat sarcoma following transfer and expression of an IL‐2 cDNA
Author(s) -
Russell Stephen J.,
Eccles Suzanne A.,
Flemming Claudia L.,
Johnson Caroline A.,
Collins Mary K. L.
Publication year - 1991
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910470213
Subject(s) - provirus , secretion , biology , paracrine signalling , transplantation , sarcoma , peripheral blood mononuclear cell , cancer research , gene , immunology , pathology , endocrinology , medicine , in vitro , receptor , genome , biochemistry
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‐2Lys 20 ) 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.