Macrophages, estrogen and the microenvironment of breast cancer

Mor, Gil; Yue, Wei; Santen, Richard J.; Gutierrez, Linda S.; Eliza, Mariel; Berstein, Lev M.; Harada, Nobuhiro; Wang, Jiping; Lysiak, Jeffrey J.; Diano, Sabrina; Naftolin, Frederick

doi:10.1016/s0960-0760(98)00143-5

Cited by 89 publications

(54 citation statements)

References 48 publications

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“…By analysing 1919 cases, Menard et al (1997) found that immune infiltration had no association with survival and prognosis of breast carcinoma patients more than 40 years of age. Furthermore, in previous studies we found that the infiltrating macrophages in breast carcinoma were a main source of estrogen, which is a major stimulus for cell proliferation and cancer progression (Mor et al, 1998). Similarly, Pollard reported that the infiltration of macrophages stimulated breast cancer progression and metastasis (Pollard, 2004), and knocking out colony-stimulating factor-1 (CSF-1, a cytokine that regulates macrophage differentiation and function) in a mouse strain inhibited breast cancer growth and metastasis.…”

Section: Tlrs Cancer Cells and The Tumor Immune Infiltratementioning

confidence: 90%

Cancers take their Toll—the function and regulation of Toll-like receptors in cancer cells

et al. 2008

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Section: Tlrs Cancer Cells and The Tumor Immune Infiltratementioning

confidence: 90%

Cancers take their Toll—the function and regulation of Toll-like receptors in cancer cells

et al. 2008

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“…In breast tissue surrounding the tumors, preadipocyte fibroblasts contain aromatase activity that can be detected by biochemical assay or immunohistochemical staining (Miller & O'Neil 1987. Normal breast tissue also contains aromatase as documented by immunohistochemistry, by demonstration of aromatase message, and by enzyme assays of cultured cells (Mor et al 1998, Brodie et al 1999.…”

Section: Physiology and Regulation Of Aromatasementioning

confidence: 99%

“…The biologic relevance of in situ estrogen production by aromatase has been demonstrated by xenograft experiments which compare tumors containing and not containing aromatase (Yue et al 1998). Human breast cancer cells transfected permanently with the aromatase enzyme are compared with cells transfected with irrelevant DNA.…”

Section: Physiology and Regulation Of Aromatasementioning

confidence: 99%

Use of aromatase inhibitors in breast carcinoma.

Santen¹,

Harvey²

1999

Endocrine-Related Cancer

146

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Aromatase, a cytochrome P-450 enzyme that catalyzes the conversion of androgens to estrogens, is the major mechanism of estrogen synthesis in the post-menopausal woman. We review some of the recent scientific advances which shed light on the biologic significance, physiology, expression and regulation of aromatase in breast tissue. Inhibition of aromatase, the terminal step in estrogen biosynthesis, provides a way of treating hormone-dependent breast cancer in older patients. Aminoglutethimide was the first widely used aromatase inhibitor but had several clinical drawbacks. Newer agents are considerably more selective, more potent, less toxic and easier to use in the clinical setting. This article reviews the clinical data supporting the use of the potent, oral competitive aromatase inhibitors anastrozole, letrozole and vorozole and the irreversible inhibitors 4-OH androstenedione and exemestane. The more potent compounds inhibit both peripheral and intra-tumoral aromatase. We discuss the evidence supporting the notion that aromatase inhibitors lack crossresistance with antiestrogens and suggest that the newer, more potent compounds may have a particular application in breast cancer treatment in a setting of adaptive hypersensitivity to estrogens. Currently available aromatase inhibitors are safe and effective in the management of hormonedependent breast cancer in post-menopausal women failing antiestrogen therapy and should now be used before progestational agents. There is abundant evidence to support testing these compounds as first-line hormonal therapy for metastatic breast cancer as well as part of adjuvant regimens in older Endocrine-Related Cancer (1999) 6 75-92 patients and quite possibly in chemoprevention trials of breast cancer.

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“…However, increased monocyte numbers have also been associated with autoimmune diseases, suggesting that the Fas/FasL system may be important not only to T cell, but also in monocyte and macrophage homeostasis (15,16). Monocytes produced in the bone morrow circulate in the peripheral blood and migrate into tissues where they differentiate, and according to their microenvironment, will exert their influence on the proliferation and apoptosis of surrounding cells, as well as controlling local immune responses (17)(18)(19). Monocytes play a major role in initiating, maintaining, and resolving host inflammatory responses by differentiating into tissue macrophages and dendritic cells and by releasing cell-signaling molecules (20).…”

mentioning

confidence: 99%

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

Mor

Sapi

Abrahams

et al. 2003

The Journal of Immunology

Self Cite

166

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The predominance of autoimmune diseases among women suggests that estrogen may modulate immune function. Monocytes and macrophages are important in initiating, maintaining, and resolving inflammatory responses through cell-signaling molecules, which control immune cell survival. One important mechanism of cell survival is mediated by the Fas/Fas ligand (FasL) system. In this study, the link between estrogen, monocytes/macrophages, and the Fas/FasL system was investigated. Estrogen treatment increased FasL expression in monocytes through the binding of the estrogen receptors (ER) to the estrogen recognizing elements and AP-1 motifs present at the FasL promoter. Furthermore, estrogen induced apoptosis in monocytes expressing ERβ, but not in monocyte-differentiated macrophages expressing ERα. The expression of either ERα or ERβ and their response to estrogen in monocytes was found to be dependent on the their stage of cell differentiation. Previously, we have shown that estrogen replacement therapy in postmenopausal women decreased the number of circulating monocytes. In this study, we have characterized the molecular mechanism by which estrogen regulates monocytes homeostasis. These findings indicate that estrogen may regulate immune cell survival through the Fas/FasL system. There is biological relevance to these findings in view of studies showing that accumulation of activated monocytes is involved in the pathogenesis of conditions such as vasculititis, arteriosclerosis, and rheumatoid arthritis.

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Macrophages, estrogen and the microenvironment of breast cancer

Cited by 89 publications

References 48 publications

Cancers take their Toll—the function and regulation of Toll-like receptors in cancer cells

Cancers take their Toll—the function and regulation of Toll-like receptors in cancer cells

Use of aromatase inhibitors in breast carcinoma.

Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes

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