Differential ability of antiestrogens to stimulate breast cancer cell (MCF-7) growth in vivo and in vitro.
We have previously described an MCF-7 breast cancer cell variant, MCF-7TAM, which is stimulated to grow in athymic mice by tamoxifen (TAM) (M. M. Gottardis and V. C. Jordan, Cancer Res., 48:5183-5187, 1988). Earlier experiments have shown that TAM exhibits some profound estrogen-like effects in mice whereas TAM is less estrogenic in the rat. The aim in these studies was to compare the ability of MCF-7TAM to grow in different host environments and to determine whether the TAM-stimulated phenotype could be maintained in vitro. Ovariectomized athymic mice and rats were implanted with 1-mm3 pieces of MCF-7TAM tumor and treated with estradiol, TAM, or control silastic capsules. After 9 weeks of growth in either species, TAM or estradiol-treated groups both had sustained growth of MCF-7TAM compared with the control groups. To determine the effects of estradiol and TAM on immune function in athymic mice, splenocytes from treated or control athymic mice, challenged with poly(I:C), were assayed for natural killer (NK) cell activity against 51Cr-labeled YAC1 target cells. Both estradiol and TAM abolished lytic activity by 12 weeks of treatment. To evaluate the role of a decrease in NK-cell activity in the host on growth of MCF-7TAM xenografts we compared the growth effects in athymic and NK-cell deficient, ovariectomized beige mice. TAM stimulated MCF-7TAM in both beige and athymic mice; however, the tumor grew more rapidly in control beige mice than in control athymic mice. This study demonstrated that TAM-stimulated growth could occur in vivo. However, TAM or 4-hydroxytamoxifen did not cause a stimulation of MCF-7TAM compared with wild-type MCF-7 cells when experiments were conducted in vitro. These studies demonstrate that a suppression immune function can facilitate the growth of MCF-7TAM in athymic animals. However, additional components of the host environment contribute to TAM-stimulated growth in vivo.
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
M M
MM
Gottardis
R J
RJ
Wagner
E C
EC
Borden
V C
VC
Jordan
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007694:Killer Cells, Natural / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol