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JCI table of contents: Dec. 3, 2007
Date:12/3/2007

e indicated that IL-6 has a role in the development of both breast and lung tumors. As discussed in the accompanying commentary by Zachary Schafer and Joan Brugge from Harvard Medical School, Boston, these data raise the possibility that IL-6targeted chemotherapeutics might be effective for the treatment of patients with certain forms of breast and lung cancer.

Massimiliano Bonaf and colleagues from the University of Bologna, Italy, showed that primary human mammospheres (MS), multicellular structures enriched in stem/progenitor cells of the mammary gland, from tumor tissue expressed higher levels of IL-6 than MS from normal breast tissue. Further in vitro analysis revealed that IL-6 induced MS self-renewal and promoted MS to adopt invasive characteristics. These effects of IL-6 were dependent on the protein Notch-3 and led the authors to conclude that, IL-6 is a potent promoter of malignant features in Notch-3expressing normal and tumor stem/progenitor cells of the mammary gland.

Similarly, a pro-tumor role for IL-6 in certain types of lung cancer is suggested by the work of Jacqueline Bromberg and colleagues at the Memorial Sloan-Kettering Cancer Center, New York. A protein known as STAT3 is persistently activated in 50% of lung cancers known as adenocarcinomas, including those that are associated with genetic mutations that result in chronic signaling through the cell surface receptor EGFR. In the study, which was performed using both mice and human lung adenocarcinoma cell lines, activated EGFR was shown to induce the expression of IL-6, which led to activation of STAT3. The clinical significance of this was suggested by the observed correlation between activated STAT3 and IL-6 expression in primary lung adenocarcinomas.

TITLE: IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland

AUTHOR CONTACT:
Massimiliano Bonaf
University of Bologna, Bologna, Italy.
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Contact: Karen Honey
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Journal of Clinical Investigation
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