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"The concept of molecular mimicry is coming to the forefront of cancer therapy — not only in terms of biomarkers, but importantly, as key features that can be exploited to improve cancer therapy and develop personalized medicine." — J. Steven Alexander, PhD, Professor in the Department of Molecular and Cellular Physiology at the LSU Health Sciences Center tumor cells that undergo EMT in response to TGF-β1 acquire properties of immune cells that essentially allow them to "disguise" themselves as dendritic cells and enter the lymphatic system. The Biochemical Investigation Researchers used a syngeneic mouse model, as well as data derived from a 3-D co-culture model. They labeled tumor cells with different EMT properties and injected them into the footpads of immuno- competent mice. At different points after the injection, they removed draining popliteal lymph nodes from the mice and analyzed the nodes using high-resolution confocal microscopy to determine whether the f luorescently labeled tumor cells were present. To complement these in vivo studies, researchers developed a 3-D invasion assay to investigate how EMT cells move toward lymphatic versus vascular endothelial cells. Research Implications Study results revealed that TGF-β1-induced EMT activates tumor cells for dendritic cell-like migration through the lymphatic system. Breast cancer cells that undergo EMT in response to TGF-β1 develop the same receptor found on activated dendritic cells, which allows tumor cells to move in a targeted fashion toward a chemokine gradient secreted by endothelial lymphatic cells. "TGF-β1 helps cancer cells escape the tumor microenvironment by making them adopt features of immune cells," Dr. Fuxe says. "In my point of view, this indicates that it may not be the EMT process per se which drives metastasis. Rather, EMT changes the properties of the tumor cells so they can sense and migrate toward inflammatory signals similar to activated immune cells. Thus, our study indicates that inflammation is a driving force for metastasis in cases where EMT has been reactivated." Dr. Fuxe says further research is necessary before clinical implica- tions can be realized. However, the study lays the groundwork for future investigation. With an end goal of developing drugs that inhibit metastasis through the lymphatic system, Dr. Fuxe hopes to learn how tumor cells navigate the lymphatic system, enter systematic circulation and establish growth at distant sites. ■ OTHER ADVANCES IN BREAST CANCER RESEARCH WHEN BREAST CANCER metastasizes, it usually spreads to the bone, brain, liver or lung, and metastasis can occur years after initial, seemingly curative treatment. Researchers in the Cancer Biology and Genetics Program at Memorial Sloan Kettering Cancer Center in New York have identifi ed a protein, cathepsin S, that may allow mammary tumor cells to pass through the blood-brain barrier and metastasize to the brain. In a study published in Nature Cell Biology, the research team uncovered the biochemical role cathepsin S is suspected of playing in metastasis. They also found that inhibiting cathepsin S production in tumor cells and microphages in the tumor microenvironment decreased the potential for metastasis, which may inform future therapies. In an article on the Memorial Sloan Kettering Cancer Center blog, lead researcher Johanna Joyce, PhD, head of the Johanna Joyce Lab, where the study took place, was enthusiastic about the fi ndings. "Brain metastasis is a devastating devel- opment of breast cancer, and the current therapeutic options are limited," she says. "To have an increased understanding of the process but also a target that we can think about going after is exciting." SPECIAL CLINICAL SECTION: ONCOLOGY M D N E W S . CO M ■ MD NEWS Long Island | 2 5