Estradiol increases IL-8 secretion of normal human breast tissue and breast cancer in vivo.
J Immunol
; 182(1): 371-8, 2009 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-19109168
ABSTRACT
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Mama
/
Neoplasias de la Mama
/
Adenocarcinoma
/
Regulación hacia Arriba
/
Interleucina-8
/
Estradiol
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Immunol
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suecia