%0 Journal Article
%T Cancer resistance of SR/CR mice in the genetic knockout backgrounds of leukocyte effector mechanisms: determinations for functional requirements
%A Anne M Sanders
%A John R Stehle
%A Michael J Blanks
%A Gregory Riedlinger
%A Jung W Kim-Shapiro
%A Arta M Monjazeb
%A Jonathan M Adams
%A Mark C Willingham
%A Zheng Cui
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-121
%X SR/CR mice were bred into individual Prf-/-, Cybb-/-, or Nos2-/- genetic backgrounds and then challenged with sarcoma 180 (S180). Their overall survival was compared to controls. The cancer killing efficiency of purified populations of macrophages and neutrophils from these immunodeficient mice was also examined.When these genetically engineered mice were challenged with cancer cells, the knockout backgrounds of Prf-/-, Cybb-/-, or Nos2-/- did not completely abolish the SR/CR cancer resistant phenotype. However, the Nos2-/- background did appear to weaken the resistance. Incidentally, it was also observed that the male mice in these immunocompromised backgrounds tended to be less cancer-resistant than SR/CR controls.Despite the previously known roles of perforin, superoxide or nitric oxide in the effector mechanisms of innate immune responses, these effector mechanisms were not required for cancer-resistance in SR/CR mice. The resistance was functional when any one of these effector mechanisms was completely absent, except some noticeably reduced penetrance, but not abolishment, of the phenotype in the male background in comparison to female background. These results also indicate that some other effector mechanism(s) of granulocytes may be involved in the killing of cancer cells in SR/CR mice.Spontaneous Regression/Complete Resistant (SR/CR) mice are a mouse model that is capable of resisting lethal challenges with a wide variety of cancers [1,2]. The resistance resides primarily in innate leukocytes consisting of granulocytes, monocytes, and natural killer cells which migrate to the site of the tumor, recognize the cancer cells via tight contact, and then destroy the tumor cells mainly through cytolysis [1,2]. The cytolysis of cancer cells in SR/CR mice was previously indicated to involve multiple effector mechanisms [1-3], a number of which are associated with innate immunity. Specifically, perforin and granzymes were detected in the peritoneal fluid and in a fra
%U http://www.biomedcentral.com/1471-2407/10/121