The effects of IL-6 on cell adhesion and e-cadherin expression in breast cancer.
Interleukin 6 (IL-6) is a pleiotropic inflammatory cytokine and its role in cancer is not yet clear. The effects of IL-6 on four breast cancer cell lines and normal mammary epithelium, cultured from milk were tested. Four different patterns of response to IL-6 were found depending on the differentiation status of the cells. In normal mammary epithelial cultures, the effects of IL-6 were mainly growth inhibitory, whereas in MCF-7, IL-6 had growth inhibitory and anti-adhesive effects. In T-47D and ZR-75-1 the anti-adhesive effects were prominent although the growth inhibitory effects were not. These anti-adhesive effects were associated with epithelioid to fibroblastoid morphological changes and a local decrease in E-cadherin expression. In the highly invasive cell line MDA-MB-231, which does not express E-cadherin, no effects of IL-6 were seen. IL-6 levels in the serum of 60 breast cancer patients were found to be increased in 27% (16/60) compared to 2% (1/50) in a control group. Furthermore, it was found that altered E-cadherin expression was seen in 69% of the primary tumours, although no significant association was found between raised serum IL-6 levels and altered E-cadherin expression. Finally IL-6 serum levels did not effect the survival of breast cancer patients. The authors therefore implicate IL-6 as a possible factor important in breast cancer progression and metastasis formation, although the clinical significance of this cytokine in breast cancer patients could not be established.
Molecular and Cell Biology Laboratory, Icelandic Cancer Society, P.O. Box 5420, Reykjavik, Iceland.
K S
KS
Asgeirsson
K
K
Olafsdóttir
J G
JG
Jónasson
H M
HM
Ogmundsdóttir
D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000097:blood*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D015820:Cadherins; D006131:Growth Inhibitors; D015850:Interleukin-6; D009363:Neoplasm Proteins