Abstract
Natural killer cell-mediated cytotoxicity (NKCC) is one of several possible immune defense mechanisms that may protect against the development of solid-tumor metastases. We have demonstrated that in vitro NKCC can be significantly impaired by both surgical stress and progressive tumor burden. Female C57BL/6 mice received a hindfoot amputation under anesthesia with Nembutal i.p. Twenty-four hr later, amputated and control groups were sacrificed, spleens were harvested, and cytotoxicity assays were performed using 51Cr-labeled Yac-1 lymphoma target cells. In amputated animals, in vitro NKCC was significantly impaired at four effectontarget ratios, decreasing by as much as 59%. Nembutal treatment alone caused no significant changes in in vitro NKCC compared to untreated controls. Tumor burden was studied by inoculating the hindfoot pads of C57BL/6 mice with 5 x 105 Lewis lung tumor cells. Animal groups were sacrificed 24 hr, 1 week, and 2 weeks after tumor inoculation, and th51 Cr release assay was performed. One day and 1 week of tumor burden mildly stimulated NKCC in vitro; after 2 weeks of tumor burden, when lung metastases were detectable, In vitro NKCC was almost totally suppressed compared with non-tumor-bearing controls. Animals bearing tumor for 1 week and then given amputations showed significantly impaired NKCC in vitro. In vivo, identical animals bearing tumor for 1 week and then given amputations on sacrifice 1 week later were found to have a 71 % incidence of lung metastases compared with 38% tumor-bearing unstressed controls. Surgical stress and progressive tumor burden independently and codependently impair NKCC in vitro; this may possibly contribute to the hypemnetastatic response observed after surgical stress in this in vivo animal model.
Original language | English (US) |
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Pages (from-to) | 3888-3891 |
Number of pages | 4 |
Journal | Cancer Research |
Volume | 44 |
Issue number | 9 |
State | Published - Sep 1 1984 |
ASJC Scopus subject areas
- Oncology
- Cancer Research