Images from research done by the Taichman Lab for its newly published paper: At left are prostate cancer cells; at right are prostate cancer cells with osteoblasts, which are cells that work together to synthesize bone. Green is the cell; blue is the nucleus; red designates Ki-67, a marker for the proliferation of cells, which increases in tumors.
Ann Arbor, Mich., Nov. 22, 2016 -– A new study led by a School of Dentistry professor advances the scientific understanding of how two types of proteins are linked to the behavior of cancer cells in bone marrow.
Research from the lab of Dr. Russell Taichman was published by Scientific Reports, an online journal covering the natural sciences. The open access site, one of the largest online journals in the world, is part of a network of publications tied to Nature, a leading international scientific journal.
Taichman, the Major Ash Collegiate Professor in the Department of Periodontics and Oral Medicine and Associate Dean for Research, is the principal investigator for the paper, “Axl is required for TGF-ß2-induced dormancy of prostate cancer cells in the bone marrow.”
Taichman and his team have been studying a protein present in the bone marrow called growth arrest specific-6 – or GAS6 – that prevents blood stem cells from dividing. It’s an important function because uncontrolled growth of stem cells can lead to serious blood disorders including leukemia. A problem arises, however, because tumor cells – prostate cancer in this study – also end up in the bone marrow, where GAS6 causes them to become dormant. In this state, tumor cells are not killed by conventional chemotherapy agents. Later, these cells can form tumors and are a major source of the relapse of breast, prostate and other cancers in the marrow.
A second family of proteins, which are better known to induce tumor dormancy in marrow, is the Transforming Growth Factor Beta family, or TGF-ß, which was characterized for the team by a collaborator, Dr. Julio Aguirre-Ghiso at the Icahn School of Medicine at Mount Sinai New York. The paper links these two sets of proliferation regulators, Taichman said. The new data suggests that exposure of tumor cells to GAS6 induces expression of TGF-ß receptors, which then induce tumor dormancy. “These results suggest that in order to effectively eliminate tumor cells in the marrow, we are going to have to treat not just one pathway, but two,” Taichman said.
Taichman notes that dentistry has a long history of studying the biology of bone and the tumors that target the bone marrow. These findings are directly applicable to understanding how blood development impacts bone development – and ultimately regeneration – and how tumor cells co-opt the normal biology for growth and survival.
Other U-M School of Dentistry researchers contributing to the new publication are Dr. Kenji Yumoto, Dr. Ann M. Decker, Dr. Younghun Jung, Jingcheng Wang and Matthew Eber (now at Wake Forest University). Other U-M contributors are Dr. Frank C. Cackowski, a hematology-oncology fellow at the Medical School, and Eunsohl Lee, an undergrad student. Also collaborating are Drs. Ana Rita Nobre and Julio A. Aguirre-Ghiso at the Icahn School of Medicine at Mount Sinai in New York.
The work is supported by the U-M MCubed Project, the National Cancer Institute, U.S. Department of Defense and the Prostate Cancer Foundation.
Read the paper at Scientific Reports here.
The University of Michigan School of Dentistry is one of the nation’s leading dental schools engaged in oral health care education, research, patient care and community service. General dental care clinics and specialty clinics providing advanced treatment enable the school to offer dental services and programs to patients throughout Michigan. Classroom and clinic instruction prepare future dentists, dental specialists, and dental hygienists for practice in private offices, hospitals, academia and public agencies. Research seeks to discover and apply new knowledge that can help patients worldwide. For more information about the School of Dentistry, visit us on the Web at: www.dent.umich.edu.
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