IL-25 causes apoptosis of IL-25R-expressing breast cancer cells without toxicity to nonmalignant cells
Journal
Science Translational Medicine
Journal Volume
3
Journal Issue
78
Pages
78ra31
Date Issued
2011
Author(s)
Abstract
As cells differentiate into tissues, the microenvironment that surrounds these cells must cooperate so that properly organized, growth-controlled tissues are developed and maintained. We asked whether substances produced from this collaboration might thwart malignant cells if they arise in the vicinity of normal tissues. Here, we identified six factors secreted by nonmalignant mammary epithelial cells (MECs) differentiating in three-dimensional laminin-rich gels that exert cytotoxic activity on breast cancer cells. Among these, interleukin-25 (IL-25/IL-17E) had the highest anticancer activity without affecting nonmalignant MECs. Apoptotic activity of IL-25 was mediated by differential expression of its receptor, IL-25R, which was expressed in high amounts in tumors from patients with poor prognoses but was low in nonmalignant breast tissue. In response to IL-25, the IL-25R on the surface of breast cancer cells activated caspase-mediated apoptosis. Thus, the IL-25/IL-25R signaling pathway may serve as a new therapeutic target for advanced breast cancer.
SDGs
Other Subjects
caspase; death receptor; interleukin 25; interleukin 25 receptor; interleukin receptor; unclassified drug; FADD protein, human; Fas associated death domain protein; interleukin 17; interleukin receptor; small interfering RNA; tumor necrosis factor receptor associated death domain protein; animal experiment; animal model; apoptosis; article; breast cancer; cancer cell; cell mediated cytotoxicity; controlled study; culture medium; enzyme activation; human; human tissue; mouse; nonhuman; priority journal; protein expression; protein function; protein protein interaction; protein secretion; signal transduction; apoptosis; breast tumor; cell line; drug effect; female; genetics; immunohistochemistry; immunoprecipitation; in vitro study; liquid chromatography; metabolism; tandem mass spectrometry; tumor cell line; Apoptosis; Breast Neoplasms; Cell Line; Cell Line, Tumor; Chromatography, Liquid; Fas-Associated Death Domain Protein; Female; Humans; Immunohistochemistry; Immunoprecipitation; Interleukin-17; Receptors, Interleukin; RNA, Small Interfering; Tandem Mass Spectrometry; TNF Receptor-Associated Death Domain Protein
Type
journal article