Aromatase activity and interleukin-6 production by normal and malignant breast tissues.

Abstract

The aromatase enzyme complex, which regulates the conversion of androstenedione to estrone, may have an important role in regulating estrogen synthesis in breast tissues. In this study the effect of tumor location on aromatase activity in adjacent tissue was examined and related to interleukin-6 (IL-6) production, which has been shown to stimulate aromatase activity in breast cancer cells. Samples of normal and malignant breast tissues were obtained from 11 women undergoing mastectomy. In 7 patients, aromatase activity was highest in the quadrant in which the tumor was located or on which the tumor impinged. Aromatase activity in tumor-bearing quadrants was significantly higher than that in adjacent and opposite quadrants. Aromatase activity and IL-6 production, expressed in terms of tissue weight, were significantly higher for tumor tissue compared with normal breast adipose tissue. A significant correlation was found between aromatase activity and IL-6 production for breast tumor tissue (rs = 0.56; P < 0.05), but not for adipose tissue from the breast quadrants. Aromatase activity and IL-6 production were also measured in tissue obtained from a normal woman undergoing reduction mammoplasty who had previously had breast augmentation by silicone injection, not contained within a capsule. In tissue from this patient there was evidence of chronic inflammation and a marked macrophage response. Aromatase activity in this tissue was considerably higher than that detected in mastectomy adipose tissue samples, and a significant correlation was found between aromatase activity and IL-6 production (rs = 0.77; P < 0.05). A preliminary study to examine the potential role of cells of the immune system in regulating breast tissue aromatase activity revealed that conditioned medium collected from macrophages and lymphocytes could markedly stimulate aromatase activity in tumor-derived fibroblasts. The results of this study confirmed that breast tumor location can influence aromatase activity in adjacent tissues and showed that aromatase activity is increased in tumor-bearing quadrants. The increased production of IL-6 by tumor tissue and its correlation with aromatase activity suggest that tumors may be the major source of IL-6, which is able to influence aromatase activity in adjacent tissues.

The interleukin 6 −174G/C Polymorphism is associated with indices of obesity in men

“…Purohit et al (1995) hypothesized that IL6 modulates the reaction of aromatase, a key regulatory enzyme for estrogen metabolism, influencing satiety and adipose tissue distribution. IL6 was also reported to be the second most secreted protein "hormone" to be released by human subcutaneous AT, supporting the hypothesis of the role of this Results are expressed as mean Ϯ SD.…”

C-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction

“…Both cytokines are expressed in, and released by, adipose tissue. [13][14][15][16] We have recently reported significant in vivo release of IL-6, but not TNF-␣, by a subcutaneous adipose tissue depot. 13 However, the relationships of circulating concentrations of TNF-␣ with obesity suggests that adipose tissue, perhaps in other sites, may contribute to circulating levels.…”

“…13 The production of IL-6, as well as systemic concentrations, increase with adiposity, and we have estimated that Ϸ30% of total circulating concentrations of IL-6 originate from adipose tissue in healthy subjects. 13 Both IL-6 and tumor necrosis factor-␣ (TNF-␣) are expressed in adipose tissue 14,15 and in vitro release of TNF-␣ by adipocytes has been reported. 16 Among the known effects of these cytokines are inhibition of insulin signaling 17 and induction of both hypertriglyceridemia 18 and endothelial activation.…”

The relationship between body fat and C-reactive protein in middle-aged Korean population

“…Since the high-sensitivity method for measuring CRP levels was introduced a few years ago, more accurate and precise relationships between CVD and CRP are being identified [1]. Adipose tissue, one of risk factors for atherosclerosis, is closely associated with inflammation by secreting proinflammatory cytokines [2,3]. Moreover, these proinflammatory cytokines control the synthesis of CRP [4].…”