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Physiological mediators of psychosocial stressor effects on the growth of a hormone-responsive mouse mammary carcinoma

University of British Columbia

This thesis investigated the role of specific immune and endocrine variables in mediating the effects of social housing condition on the growth of the transplantable androgen-responsive Shionogi mouse mammary carcinoma (SC 115). Mice were reared either individually (I) or group(G) housed, and then either remained in their rearing groups (II, GG) or were rehoused (IG, GI). Splenic NK cell activity of tumor cell- and vehicle-injected mice from the 4 experimental housing groups was investigated at 1 d post tumor cell- or vehicle-injection. Splenic NK cellactivity was suppressed in tumor cell-injected mice compared with vehicle-injected controls. Overall, mice of the GI group had significantly greater splenic NK cell activity than mice of the IG group. NK cell activity of tumor infiltrating lymphocytes in mice of the GI and IG groups was then investigated using a modification of the sponge allograft model. Overall, NK cell activity was greater in tumor cell-injected than in vehicle-injected sponges, and was greater in tumor cell-injected sponges of mice in the GI group than in those of mice in the IG group. Finally, the effects of modulating in vivo levels of NK cell activity on tumor growth rate were assessed. Injection ip of polyinosinic:polycytidylic acid (poly I:C, 100 Al lmg/m1) or of anti-asialo GM1(ASGMi, 100 IA of a 1:5 dilution) every 5 d for 2 wk maintained stimulation or suppression (respectively) of splenic NK cell activity relative to that in saline-injected control mice, and had no effect on tumor growth rate in mice of the IG group. In mice of the GI group, stimulation of NKcell activity by poly I:C was accompanied by a significant stimulation of tumor growth rate compared with that of ASGMi-injected or control mice. These studies suggest that NK cells may play an important role in mediating the stimulation of SC 115 tumor growth rate in mice of the GI group. In addition, the possibility that 1) selection for a slow growing, hormone-independent phenotype, or 2) alterations in plasma hormone levels may mediate the differential tumor growth rates was examined. Slow growing tumors from mice of the IG group had a morphological appearance similar to that of mice from the other experimental groups and dissimilar to that of slow growing androgen-independent tumors grown in females. Further, tumor cells from mice of the IG group showed greater proliferation in response to in vitro stimulation withdihydrotestosterone or hydrocortisone than tumor cells from mice of the GI group. In addition, mice of the GG and II groups had elevated basal levels of plasma testosterone at 1 d which declined significantly by 3d. Mice of the IG group had low basal plasma testosterone levels, whereas mice of the GG group had elevated basal plasma testosterone levels at all time points. In contrast, basal plasma corticosterone levels were significantly greater in mice of the IG group than in mice of all other groups at 1, 3 and 7 d. These data suggest that altered plasma levels of steroid hormones may also, in part, mediate the effects of psychosocial stressors on the differential tumor growth rate observed in this model, whereas selection for a subpopulation of SC 115 cells with altered hormone responsiveness is likely not involved.

Thesis/Dissertation

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2008-10-14

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http://hdl.handle.net/2429/2637

Anatomy, Cell Biology and Physiology

University of British Columbia

UBCV

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