How Breast Tumor Cells Become Metastatic

How Breast Tumor Cells Become Metastatic

Most cancer deaths result from metastasis—when cancer cells leave primary breast tumors and travel through the blood vessels to distant organs to initiate new tumors. Only those rare breast-cancer cells known as cancer stem cells can complete the entire metastatic process.

In a study published online on December 15 in Nature Communications, using mouse models of breast cancer and high resolution intravital microscopy, Albert Einstein College of Medicine’s Maja Oktay, M.D., Ph.D., and John Condeelis, Ph.D., showed how certain breast-tumor cells are transformed into cancer stem cells. Contact with macrophages triggers a signaling pathway in tumor cells called Notch, which is normally active during embryonic development. The researchers found that the vascular “doorways” allowing cancer cells to enter blood vessels also help induce “stemness” in tumor cells due to their high concentrations of macrophages. (Such a doorway is referred to as a tumor microenvironment of metastasis, or TMEM; in previous work, the Condeelis lab found that tumors with high numbers of TMEM doorways are more likely to metastasize compared to tumors with fewer TMEM doorways). The researchers observed that cancer stem cells gather around tumor regions rich in TMEM doorways and that the density of TMEM doorways within breast tumors positively correlates with the proportion of stem cells observed in breast cancers from patients. The findings suggest that targeting these macrophage-tumor cell interactions and the Notch pathway could be an effective strategy for preventing breast-cancer metastasis.

Dr. Oktay is professor of pathology and of anatomy and structural biology and co-director of the Tumor Microenvironment and Metastasis Program in the Albert Einstein Cancer Center. Dr. Condeelis is professor and co-chair of anatomy and structural biology, co-director of the Gruss Lipper Biophotonics Center and the Integrated Imaging program. He also holds the Judith and Burton P. Resnick Chair in Translational Research. The third co-corresponding senior author is Lalage Wakefield, D.Phil., from the National Cancer Institute.

Recently, Dr. Condeelis received the I.J. "Josh" Fidler Innovation in Metastasis Research Award from the Metastasis Research Society for his significant contributions to metastasis research.

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