Estradiol increases IL-8 secretion of normal human breast tissue and breast cancer in vivo.
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.
Bendrik
Christina
C
Linköping University, Faculty of Health Sciences, Division of Oncology, University Hospital, Linköping, Sweden.
Dabrosin
Charlotta
C
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001940:Breast / Q000276:immunology* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004958:Estradiol / Q000097:blood / Q000502:physiology*; D005110:Extracellular Space / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D017698:Postmenopause / Q000276:immunology; D017697:Premenopause / Q000276:immunology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology*
D016209:Interleukin-8; D004958:Estradiol