Researchers learn how signaling molecule orchestrates breast cance...( NEW YORK April 3 2008 -- A study led...),Health

NEW YORK, April 3, 2008 -- A study led by researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) has uncovered how breast tumors use a particular type of molecule to promote metastasis -- the spread of cancer cells. Metastasis is the cause of approximately 90 percent of all cancer-related deaths. The study is published in the April 4, 2008, issue of Cell.

The work examines how cells in the body communicate with each other through cytokines, signaling molecules that direct a wide range of activities such as cell growth and movement. One important cytokine -- transforming growth factor -a (TGF-a) -- normally suppresses tumor development. However, according to the findings, cancer cells in humans are able to misuse these cytokines for their own gain by compelling TGF-a to enhance a tumor's ability to spread instead of suppressing it.

Using computer-based analysis to classify patient tumor samples based on their levels of TGF-a, the researchers observed that about half of all breast tumors contained active TGF-a. The affected tumors were found to be more aggressive and more likely to metastasize to the lung during the course of the patients' disease.

Using mice for their next set of experiments, the researchers discovered that TGF-a prompts breast cancer cells to make a second cytokine, known as angiopoietin-like 4 (ANGPTL4), which enhances the ability of the cancer to spread to the lungs through the blood circulation. The results show that the breast cancer cells use ANGPTL4 to break down the thin capillaries of the lung, thus facilitating their escape into the lung tissue.

"Our work shows that TGF-a enhances human breast cancer metastasis and reveals how tumor cells learn to exploit cytokines by making them work as a relay system to promote the spread of breast cancer," said the study's senior author, Joan Massagu, PhD, Chairman of the Cancer Biology and Genetics Program at MSKCC and a Howard Hughes Medical Institute invest
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