Koch, Janne2; Hau, Jann3; Jensen, Henrik Elvang4; Rieneck, Klaus1
1 Klinisk Immunologisk Afdeling. Blodbanken og Vævstypelaboratoriet, Diagnostisk Center, Rigshospitalet, The Capital Region of Denmark2 Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Institute of Veterinary Pathology, Faculty of LIFE Sciences, University of Copenhagen, Frederiksberg, Denmark firstname.lastname@example.org Department of Experimental Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.4 Institute of Veterinary Pathology, Faculty of LIFE Sciences, University of Copenhagen, Frederiksberg, Denmark.
AIM: To induce cancer resistance in wild-type mice and detect if the resistance could be inherited to the progeny of the induced resistant mice. Furthermore to investigate the spectrum and immunology of this inherited cancer resistance. MATERIALS AND METHODS: Resistance to with live S180 cancer cells in BALB/c mice was induced by immunization with inactivated S180 cancer cells. The immunization was performed by either frozen/thawed or irradiated cancer cells or cell-free ascitic fluid (CFAF). RESULTS: In all instances the induced resistance was demonstrated to be inheritable. The phenotype was named HICR (heritable induced cancer resistance) and was defined as primary resistant progeny from mice immunized with frozen/thawed or irradiated S180 cells or CFAF obtained from mice with S180 induced ascites. Notably, this resistance was transferred from both male and female mice to the offspring of the immunized mice for at least two generations. Although inheritable, the frequency of cancer-resistant pups was lost over a few generations. Cells from the J774A.1 and RAW cancer cell lines did not induce inheritable cancer resistance, and C57BL/6 mice could not pass on cancer resistance fluorescence-activated cell sorting (FACS) analyses of the peritoneal cells revealed an increased fraction of macrophages. In necropsies of resistant mice no histological signs of cancer or other disease was found. CONCLUSION: Only materials derived from S180 cells could give rise to HICR mice. The molecular basis of the resistance is unknown but may involve epigenetic mechanisms. Other examples of inheritability of acquired phenotypic changes exist but, to our knowledge, this is the first demonstration of acquired, inherited cancer resistance.
Anticancer Research, 2014, Vol 34, Issue 11, p. 6315-25