Estrogenic Regulation of Host Immunity against an Estrogen Receptor–Negative Human Breast Cancer
| Autor: | D. Mark Estes, Hui-Qun Wang, Ngozi A. Duru, Dennis B. Lubahn, Barbara M. Judy, Leoncio A. Vergara, Edward M. Curran |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Cancer Research medicine.drug_class medicine.medical_treatment Transplantation Heterologous Estrogen receptor Breast Neoplasms Mice SCID Biology Mice Breast cancer Immune system Tumor Cells Cultured medicine Animals Humans Cell Proliferation Mice Knockout Innate immune system Estradiol Cancer medicine.disease Immunity Innate Mice Inbred C57BL Transplantation Cytokine Receptors Estrogen Oncology Estrogen Immunology Cytokines Female |
| Zdroj: | Clinical Cancer Research. 12:5641-5647 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-05-1117 |
| Popis: | Purpose: The risk of developing breast cancer is positively correlated with exposure to increased levels of estrogen and/or an increased duration of estrogen exposure. Many different mechanisms have been proposed to explain the association of estrogens with breast cancer risk; however, the well-documented immune modulatory properties of estrogen have received little attention. In part, this is due to a lack of suitable models for studying this relationship.Experimental Design: We have developed an animal model using estrogen receptor (ER)-negative human breast cancer cell line, MDA-MB-468, xenografted into severe combined immunodeficient (SCID) mice. We also generated the ER-α knockout (ER-αKO) mice on the SCID background and then tested the ability of 17β-estradiol to stimulate growth of xenografted ER-negative human breast cancer tumors in wild-type and ER-αKO SCID mice. We quantified vascularization of tumors, macrophage recruitment to the tumor site by immunocytochemistry, and inflammatory cytokine production.Results: We show that estrogen treatment of C57BL/6/SCID mice promotes the growth of xenografted ER-negative tumors in wild-type mice and this estrogen-induced tumor growth is abrogated in ER-αKO mice. Tumor neovascularization of estrogen-treated mice was unchanged versus control; however, estrogen treatment of the C57BL/6/SCID host suppressed macrophage recruitment to and inflammatory cytokine production at the tumor site.Conclusions: These data are consistent with estrogen modulation of the inflammatory response as a contributing factor in estrogen-stimulated growth of an ER-negative tumor. This effect on the host innate immune response was mediated by ER-α. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|