Estradiol increases IL-8 secretion of normal human breast tissue and breast cancer in vivo.
نویسندگان
چکیده
IL-8 or CXCL8 has been associated with tumor angiogenesis, metastasis, and poor prognosis in breast cancer. Estrogen is crucial in breast carcinogenesis and tumor progression. Whether sex steroids affect IL-8 secretion of normal breast tissue or breast cancer is not known. Several cell types in a tissue secrete IL-8. Hence, regulatory mechanisms of IL-8 need to be investigated in whole tissue. We used microdialysis to sample IL-8 in normal human breast tissue in situ in pre- and postmenopausal women, preoperatively in breast cancers of women, and in experimental breast cancer in mice. We found a significant positive correlation between IL-8 and estradiol in normal breast tissue and hormone-dependent breast cancer in vivo. Ex vivo, estradiol exposure increased the IL-8 secretion of normal whole breast tissue in culture. In experimental breast cancer, estradiol increased IL-8 whereas the anti-estrogen tamoxifen inhibited the secretion of IL-8 both in vitro and extracellularly in vivo in tumors of nude mice. An anti-IL-8 Ab inhibited endothelial cell proliferation induced by cancer cell produced IL-8 and tumors with low IL-8 levels exhibited decreased angiogenesis. Our results strongly suggest that estradiol has a critical role in the regulation of IL-8 in normal human breast tissue and human breast cancer. IL-8 may present a novel therapeutic target for estrogen driven breast carcinogenesis and tumor progression.
منابع مشابه
Effect of 17-? Estradiol on the Expression of Inducible Nitric oxide Synthase in Parent and Tamoxifen Resistant T47D Breast Cancer Cells
Indirect evidence suggests that estrogen is involved in the etiology of breast cancer. Estrogen is also thought to modulate nitric oxide (NO) in human breast tumor tissue via regulation of inducible nitric oxide synthase (iNOS). Objectives of this study were to determine whether estradiol (E2) affects iNOS expression level in breast cancer cells and to study the effect of various concentrations...
متن کاملEffect of 17-? Estradiol on the Expression of Inducible Nitric oxide Synthase in Parent and Tamoxifen Resistant T47D Breast Cancer Cells
Indirect evidence suggests that estrogen is involved in the etiology of breast cancer. Estrogen is also thought to modulate nitric oxide (NO) in human breast tumor tissue via regulation of inducible nitric oxide synthase (iNOS). Objectives of this study were to determine whether estradiol (E2) affects iNOS expression level in breast cancer cells and to study the effect of various concentrations...
متن کاملInjectable Estradiol Valerate, as a Substitute for Estradiol Pellets in Breast Cancer Animal Model
The ability to maintain and study human tissues in in-vivo environment has proved to be a valuable tool in breast cancer research for several decades. The most widely tissues have been xenografts established human breast cancer cell lines into athymic nude mice. The aim of this study was to provide a new accurate and affordable method for the establishment of breast cancer xenograftin nude mice...
متن کاملEstradiol affects extracellular leptin:adiponectin ratio in human breast tissue in vivo.
CONTEXT Exposure to sex steroids is associated with increased breast cancer risk, and adipokines, leptin and adiponectin have been implicated in cancer progression. However, it is not known whether sex steroids affect adipokine secretion in breast tissue. OBJECTIVE To elucidate the role of estrogen and tamoxifen on adipokine release in normal human breast tissue and breast cancer. SETTING A...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 182 1 شماره
صفحات -
تاریخ انتشار 2009