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In vitro and in vivo interaction between murine fibrosarcoma cells and natural killer cells
Abstract:
Murine fibrosarcoma cells were examined for sensitivity to killing by natural killer (NK) and natural cytotoxic lymphocytes from mouse spleens. These tumor cell lines were sensitive to killing by effector cells which were nonadherent to plastic or nylon wool, Thy-1 negative, asialo-GM1 negative, and present in the spleens of beige mice, nude mice, and A/J mice, as well as in the spleens of normal syngeneic and allogeneic control mice. This indicates that the cytotoxic effects were due to natural cytotoxic lymphocytes rather than to NK lymphocytes, T-cells, or macrophages. Although the fibrosarcoma cells were not killed in vitro by endogenous NK cells, these tumor cells were able to "cold target" compete for Yac-1 (an NK-sensitive target) killing and to bind to asialo-GM1-positive, nonadherent spleen lymphocytes in a target cell binding assay. This suggests that the fibrosarcoma cells were recognized by NK cells. In addition, these cell lines were killed in a 4-h NK cytotoxicity assay by polyinosinic-polycytidylic acid-activated effector lymphocytes. The interaction between NK cells and the murine fibrosarcoma cells may have in vivo significance. When syngeneic mice were treated with anti-asialo-GM1 serum to eliminate NK activity and then given i.v. injections of the fibrosarcoma cells, many more lung tumors developed than in control animals. The structural basis for the recognition of the murine fibrosarcoma cells by the NK effector cells is not known. However, laminin may be involved. When the fibrosarcoma cells, which have receptors for the laminin molecule, were preincubated with laminin, they were reduced in their ability to compete for the killing of Yac-1 cells by the NK effectors and had reduced capacity to bind to NK cells in a target cell binding assay.
Insights
Murine fibrosarcoma cells are killed by natural cytotoxic lymphocytes, not NK cells, but are recognized by NK cells. Laminin may mediate this interaction, impacting tumor growth in vivo.
Area of Science:
- Immunology
- Cancer Biology
Background:
- Natural killer (NK) cells and natural cytotoxic (NC) lymphocytes are key immune players.
- Murine fibrosarcoma cell lines were investigated for their susceptibility to these effector cells.
Purpose of the Study:
- To differentiate between NK and NC lymphocyte-mediated killing of fibrosarcoma cells.
- To explore the interaction between fibrosarcoma cells and NK cells, and its in vivo implications.
Main Methods:
- Phenotypic characterization of effector cells (plastic adherence, Thy-1, asialo-GM1).
- In vitro cytotoxicity assays using fibrosarcoma cell lines and Yac-1 targets.
- In vivo studies involving tumor cell injection in NK-depleted mice.
- Laminin pre-incubation experiments to assess binding and competition assays.
Main Results:
- Cytotoxicity was primarily mediated by NC lymphocytes, characterized as nonadherent, Thy-1 negative, and asialo-GM1 negative.
- Fibrosarcoma cells, while not killed by endogenous NK cells, were recognized by them, evidenced by cold target competition and binding assays.
- Elimination of NK activity in vivo led to increased lung tumor formation after fibrosarcoma cell injection.
- Pre-incubation with laminin reduced fibrosarcoma cell recognition and binding by NK cells.
Conclusions:
- Murine fibrosarcoma cells are primarily sensitive to natural cytotoxic lymphocytes.
- Natural killer cells recognize fibrosarcoma cells, and this interaction has in vivo relevance for tumor progression.
- Laminin may play a role in the recognition mechanism between NK cells and fibrosarcoma cells.