Tumorigenicity and lysis by natural killers.

Abstract

Detailed analysis of the natural killer (NK) activity directed at nontumorigenic cell lines and their transformed tumorigenic derivatives has revealed a paradox. On the one hand, a correlation has been found between the tumorigenic potential of chemically transformed fibroblast cell lines and their sensitivity to NK cells in vitro. Nontransformed cells (N-type cell lines) and cells tumorigenic in normal mice (C-type cell lines) are resistant to NK-mediated lysis. In contrast, cell lines that are tumorigenic in ATxFL mice (these mice are very low in NK activity), but not in normal mice (I-type cell lines) are sensitive to NK-mediated lysis. These findings support the concept that NK activity is involved in host surveillance against tumors. On the other hand, NK-resistant fibroblasts, whether taken directly form animals or derived as tumorigenic or nontumorigenic cell lines, compete with NK-sensitive target cells to inhibit their lysis by NK effectors. Not only are both NK-sensitive and -resistant cells recognized by NK effectors but both receive lytic signals from NK effector cells. Target cell resistance is a result of a protein synthesis-dependent mechanism that prevents lysis such that in the presence of inhibitors of protein synthesis all fibroblasts tested are NK sensitive. Those fibroblasts that are normally sensitive to NK-mediated lysis must be deficient in their ability to produce or respond to this counterlytic mechanism. These findings are in contrast with the general findings when lymphoid cells are studied as NK targets where sensitivity appears to be a result of recognition by NK effectors. Because our findings show that transformed and normal cells express the same recognition determinants, in order for NK activity to play an important in vivo role in tumor surveillance, a mechanism must operate to permit NK effectors to find their targets in vivo. In the absence of a special discrimination mechanism, the killing of NK-sensitive transformants that arise autochronously would be less than optimal as a consequence of competition by the normal, NK-resistant, cells.

DNA virus‐transformed hamster cell – host effector cell interactions: Level of resistance to cytolysis correlated with tumorigenicity

“…Similar correlations between neoplastic cell tumorigenic potential and susceptibility to destruction by nonspecific host effector cells have been made by others studying different tumor models (Herberman and Holden, 1978;Stutman et d., 1980;Tai et al, 1980;Collins et al, 1981). In most other experimental models, however, some form of selection pressure (usually in vivo tumor cell transplantation) was required for the generation of cells resistant to effector cell-induced lysis.…”

RNA-Dependent Replication and Transcription of Hepatitis Delta Virus RNA Involve Distinct Cellular RNA Polymerases

“…Huh7 cells (34) were cultured at 37°C in Dulbecco modified Eagle medium (DMEM) supplemented with 10% fetal bovine serum, 100 IU of penicillin per ml, 100 mg of streptomycin per ml, 2 mM L-glutamate, and 1% nonessential amino acids (complete DMEM). BC10 M/E cells, a mouse cell line (10), were cultured at 37°C in DMEM supplemented with 10% fetal bovine serum, 100 IU of penicillin per ml, and 100 mg of streptomycin per ml. The BC10ME-derived permanent cell line BCHAWT, which expresses an ␣-amanitin-resistant mutant pol II, was selected in G418 at 600 g/ml after transfection with plasmid pHAWT (see below).…”

Modifications of the Human Immunodeficiency Virus Envelope Glycoprotein Enhance Immunogenicity for Genetic Immunization

“…Cells were incubated for 7 days in the presence of interleukin 2 (10 U/ml) and either irradiated peptide-pulsed splenocytes from naive mice or an irradiated stable cell line expressing the full-length gp160 BC-env/rev (18). Three types of target cells were used: peptide-pulsed P815 cells (ATCC TIB64), BC10ME cells stably expressing gp160, and BC10ME cells (11) pulsed with peptides derived from gp160 sequence. Target cells were labeled with 51 Cr for 90 min and washed three times with RPMI 1640 medium with 10% fetal bovine serum, 2 mM glutamine, 5 ϫ 10 Ϫ5 M ␤-mercaptoethanol and amphotericin (Fungizone) (250 U/ml), and resuspended in this medium.…”