The American Cancer Society predicts that 40,000 American women will die from breast cancer this year. Most of those deaths will occur due to cells from the primary tumor that spread to other parts of the body-the process known as metastasis. Now, the National Cancer Institute, part of the National Institutes of Health (NIH), has awarded a $10 million grant to researchers at Albert Einstein College of Medicine of Yeshiva University to fund research into how breast cancer cells move and spread in the body, and how to predict which breast cancer tumors will metastasize.
"The main clinical problem is that there is no widely reliable test to determine the likelihood that metastasis will occur in an individual breast-cancer patient," said John Condeelis, Ph.D., the principal investigator on the grant. "Current tests focus on indirect measures-such as biomarkers indicating the growth of the primary tumor-that are not directly related to metastasis. We're trying to change that." Dr. Condeelis is professor and co-chair of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center and the Judith and Burton P. Resnick Chair in Translational Research at Einstein.
Over the past 10 years, Dr. Condeelis and his colleagues at the Tumor Microenvironment and Metastasis Program at the NCI-designated Albert Einstein Cancer Center, have studied how cancer cells move and spread. The researchers use intravital imaging, a technology that allows them to track individual cells and molecules moving within living animals in real time. Their studies of the molecular mechanisms underlying metastasis have revealed the complex cellular cross-talk that pulls and pushes certain primary tumor cells, helping them penetrate blood vessels, where they are carried by the bloodstream to other parts of the body.
The Einstein scientists have already shown that tumor cells "primed" to metastasize secrete a protein that attracts immune cells called macrophages. Tumor cell/macrophage pairs then migrate toward nearby blood vessels, drawn by endothelial cells that make up the blood-vessel wall. Most significantly, they have found that the close proximity in breast cancer tissue of a trio of cells-a tumor cell, a macrophage and an endothelial cell-is a sign that breast cancer metastasis may occur. This trio of cells is called a tumor microenvironment of metastasis, or TMEM.
The Einstein researchers have developed a test that counts the number of TMEMs within a given portion of biopsy tissue: the more TMEMs present, the greater the likelihood that the tumor will metastasize. A recent study in the Journal of the National Cancer Institute found that the TMEM test was more accurate than currently marketed tests in predicting whether breast tumors will spread.
The new NIH grant will help Dr. Condeelis and his colleagues deepen their insights into metastasis. In particular, the researchers will study the various subpopulations of macrophages that are present in primary and metastatic tumors. They hope to determine how these macrophage subpopulations differentially affect three key processes involved in cancer metastasis: intravasation (when cells from the primary tumor penetrate blood vessels), extravasation (when bloodborne tumor cells exit blood vessels after being carried to distant parts of the body) and angiogenesis (the formation of blood vessels to nourish growing tumors). In addition to Dr. Condeelis, the project leaders of the program project grant are Jeffrey Pollard, Ph.D., Richard Stanley, Ph.D., Dianne Cox, Ph.D., Jeffrey Segall, Ph.D., Jon Backer, M.D., and Anne Bresnick, Ph.D.
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