Signaling Molecule Selectively Kills Breast Cancer Cells
Signaling Molecule Selectively Kills Breast Cancer Cells
Normal breast cells (mammary epithelial cells, or MECs) secrete a signaling molecule that kills breast cancer cells but does not harm healthy cells, researchers have found. The signaling molecule, known as interleukin-25 (IL-25), binds to receptors on the surface of breast cancer cells and triggers cell death. The findings appeared in Science Translational Medicine on April 13.
Dr. Saori Furuta of Lawrence Berkeley National Laboratory (LBNL) and her colleagues used a three-dimensional (3D) cell-culture system to study the growth and development of normal MECs and breast cancer cells. The 3D culture system, which simulates the structure of normal breast tissue, was developed in the laboratory of Dr. Mina Bissell of LBNL. She co-led the study with Dr. Wen-Hwa Lee of the University of California, Irvine.
The researchers identified six molecules produced by normal breast cells grown in 3D culture that either killed breast cancer cells or suppressed their growth. Of those six molecules, IL-25 had the most potent cell-killing (cytotoxic) effects on breast cancer cells grown in the 3D system.
“The cytotoxic activity of IL-25 was restricted to cancer cells that express the receptor IL-25R on the cell surface,” said Dr. Furuta. Additional experiments showed that, when IL-25 binds to its receptor, it sets off a process known as programmed cell death, or apoptosis. The body normally uses this process to eliminate unneeded or abnormal cells.
“IL-25 is naturally produced by healthy breast tissue and thus could be a natural defense mechanism against cancer,” Dr. Furuta noted.
Injecting mice with IL-25 once a day for 1 month dramatically slowed the growth of tumors formed by implanting human breast cancer cells in the mice but did not affect healthy breast tissue or other body tissues that the researchers examined.
The researchers also analyzed 69 human breast cancer biopsy samples and found that 19 percent of those samples were IL-25R-positive. “Importantly, these IL-25R-positive tumors were highly invasive and correlated to poor clinical outcome of patients,” Dr. Furuta said.
“These data suggest strongly that the IL-25/IL-25R signaling pathway may provide novel targets for treating aggressive breast cancers” that express the IL-25 receptor, the study authors conclude.
The researchers have patented their findings and are in the process of transferring the technology to a pharmaceutical company for further development, Dr. Furuta explained.
Also in the News: ASCO Recommends Tumor Testing for Some Lung Cancer Patients
The American Society of Clinical Oncology (ASCO) has issued a Provisional Clinical Opinion (PCO) recommending that patients with advanced non-small cell lung cancer have their tumors tested for mutations in the gene that encodes epidermal growth factor receptor (EGFR) prior to taking drugs that inhibit signaling from EGFR as a first-line therapy. Patients whose tumors test negative for these mutations may benefit more from chemotherapy than from an EGFR inhibitor, such as erlotinib (Tarceva) or gefitinib (Iressa), according to the April 11 PCO.
“For patients who do not have the [EGFR] mutation, giving erlotinib first is not the right thing to do,” co-author Dr. Giuseppe Giaccone, chief of the Medical Oncology Branch at NCI’s Center for Cancer Research, said in a statement. “It does not work as well for those patients, and we may be losing the opportunity to give chemotherapy, which could be more effective.”
The PCO, which is intended to provide direction to doctors, is based on the results of five phase III clinical trials. At ASCO’s request, NCI’s Physician Data Query (PDQ) Adult Treatment Editorial Board provided a written analysis of the results of one of the trials, the IPASS study.
NCI Cancer Bulletin for April 19, 2011 - National Cancer Institute
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