Inhibition of IL-6+IL-6 soluble receptor-stimulated aromatase activity by the IL-6 antagonist, Sant 7, in breast tissue-derived fibroblasts

Purohit, Atul; Singh, Ajit; Ghilchik, M.W.; Serlupi-Crescenzi, Ottaviano; Reed, Michael J.

doi:10.1038/sj.bjc.6600785

Cited by 24 publications

(23 citation statements)

References 42 publications

(35 reference statements)

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“…All the different cell types that exist in normal breast tissue and breast cancer including tissue macrophages and lymphocytes can regulate the enzymes involved in estrogen formation and inactivation. Several cytokines secreted by these cell types on a local level have been shown to influence the expression of 17 -HSD, estrone sulphatase and aromatase (Turgeon et al 1998, Purohit et al 2002, 2003. This complex regulation necessitates research on whole tissue, preferably in vivo, rather than cell culture studies.…”

Section: Discussionmentioning

confidence: 99%

“…One microdialysis catheter was placed in the upper lateral quadrant of the left breast and directed towards the nipple as previously described (Dabrosin et al 1997a, 1997b, Dabrosin 2001, 2003. To be able to compare tissue levels collected by the microdialysis technique a reference catheter was placed in abdominal subcutaneous fat lateral to the umbilical region.…”

Section: Experimental Designmentioning

confidence: 99%

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Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle

Dabrosin

2005

Journal of Endocrinology

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Estrogen exposure is a major risk factor for breast cancer. Tissue estrogen originates from the ovaries but a significant portion is also produced by enzyme activity locally in the breast itself. How these enzymes are regulated is not fully understood. The extracellular space, where the metabolic exchange and cell interactions take place, reflects the environment that surrounds the epithelium but there has been no previous study of hormone concentrations in this compartment. In the present study microdialysis was used to measure extracellular estrogen concentrations in breast tissue and abdominal subcutaneous fat in 12 healthy women in vivo. It was found that women with high plasma progesterone levels had significant increased levels of estradiol in breast tissue compared with fat tissue (breast tissue 168 6 pM; subcutaneous fat, 154 5 pM; P<0·05), whereas women with low plasma progesterone exhibited no difference. Moreover, there was a significant correlation between local breast tissue estradiol and plasma progesterone levels (r=0·709, P<0·01). There was no difference in estrone sulphate in breast and fat tissue regardless of progesterone levels. Estrone was not detectable. The results in this study suggest that progesterone may be one regulator in the local conversion of estrogen precursors into potent estradiol in normal breast tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle

Dabrosin

2005

Journal of Endocrinology

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“…Miller et al (1997) reported that both aromatase mRNA and STAT nuclear binding showed positive correlations with aromatase activity in vitro and that tumor extracts could induce aromatase in breast fibroblasts, perhaps due to the presence of IL-6. Purohit et al (2003) showed that IL-6 together with its soluble receptor stimulated aromatase activity in fibroblasts isolated from normal breast tissue, and that this induction was blocked by a receptor-binding inactive mutated form of IL-6.…”

Section: Estrogen-adipokine Interactionsmentioning

confidence: 99%

Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression

Vona-Davis

Rose²

2007

Endocr Relat Cancer

443

359

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Adipokines (leptin, adiponectin, and hepatocyte growth factor (HGF)) secreted from adipose tissue have come to be recognized for their contribution to the mechanisms by which obesity and related metabolic disorders influence breast cancer risk. In this review, we discuss the direct and indirect effects of these protein factors on the biological and clinical aspects of breast cancer biology, and emphasize their distinctive modes of action through endocrine-, paracrine-, and autocrine-mediated pathways. The stimulatory effects of leptin on breast cancer growth were considered to occur primarily via activation of the estrogen receptor; however, new evidence suggests that leptin may be acting on downstream cell signaling pathways in both estrogendependent and -independent cell types. Another secretory adipokine, HGF, may act largely not only to promote tumor cell invasion, but also to enhance tumor growth indirectly by stimulating angiogenesis. In contrast, adiponectin, an endogenous insulin sensitizer, exerts a direct growthinhibitory effect on tumor cells by downregulating cell proliferation and upregulating apoptosis, and also inhibits tumor-related angiogenesis.

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“…It was demonstrated in studies using malignant human breast tissue that aromatase activity in adipose tissue may have a close association with the cells of the immune system, particularly macrophages and the related cytokines (42,43). Furthermore, the association between elevated aromatase levels and subclinical inflammation was more prominent in the breast tissue of most overweight and obese women (43).…”

Section: Immune Modulations Of Aromatase Inhibitorsmentioning

confidence: 96%

Immunomodulatory effects of anti-estrogenic drugs

Ray¹,

M²

2012

Acta Pharmaceutica

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Immunomodulatory effects of anti-estrogenic drugsThere are substantial experimental, epidemiological and clinical evidences that show that breast cancer pathology is influenced by endogenous estrogens. This knowledge is the foundation upon which endocrine deprivation therapy has been developed as a major modality for the management of breast cancer. Tamoxifen, which functions as a competitive partial agonist-inhibitor of estrogen at its receptor, has been widely used for more than three decades for adjuvant endocrine treatment in breast cancer. Currently, other effective drugs for endocrine therapy include raloxifene, different aromatase inhibitors (particularly third-generation agents) and luteinizing hormone-releasing hormone agonists. In recent years, a growing body of evidence suggests that these drugs can also act as immune modulators by altering the function of various leukocytes and the release of different cytokines. Moreover, there is evidence that anti-estrogens may prove to be beneficial in the treatment or prevention of some autoimmune diseases due to their effects on immune function. However, their immunopharmacological aspects in the present state of knowledge are not precisely comprehensible. Only a clear pathophysiological understanding could lead to an efficient strategy for breast cancer prevention and decrease in the mortality due to this disease.

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Inhibition of IL-6+IL-6 soluble receptor-stimulated aromatase activity by the IL-6 antagonist, Sant 7, in breast tissue-derived fibroblasts

Cited by 24 publications

References 42 publications

Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle

Increased extracellular local levels of estradiol in normal breast in vivo during the luteal phase of the menstrual cycle

Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression

Immunomodulatory effects of anti-estrogenic drugs

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