HEALTH & FITNESS ORTHODONTICS Controlling Cancer Cells ADULTS & CHILDREN Weizmann aims to slow metastasis. Rehovot, Israel Steven M. Lash, DDS, MS Rebecca L. Rubin, DMD, MS M 248-851-7272 6177 Orchard Lake Road, West Bloomfield, Michigan www.lashorthodontics.corn American Association of Orthodontists 1284640 Drs. Purcell, Sayegh & Zmmy Aleard Certified Family Medicine Specialisis Anthony J. Sayegh, D.O. Family Medicine Kelly Purcell, D.O. Family Medicine Matthew C. Zimny, D.O. Family Medicine *Specializing in All Aspects of Pediatric, Adult, and Geriatric Medicine including... • • • • Annual Physicals School/Sports Physicals Gynecologic Care Sick Visits *Same Day Appointments Available* EH EY1 MaPie Rd. BEAUMONT MEDICAL STAFF MEMBERS 4 Mlle Rd. :106311 14 Mile ltd. in Newberr 11111°. 56 3 11 Square (I Idler'. Shopping (:enn.r) (248) 960-3727 12 Mile Rd. Rd. PI 13Mile 111111 ■ . 1 :01* vow- September 27 • 2007 ►►m► iN nien ► e. (. ■► •1I11" and Week•ial la ► fir are aV ► lla ► le etastasis — when can- cer cells dissociate from the original tumor and migrate via the blood stream to colo- nize distant organs — is the main cause of cancer death. A team of scientists at the Weizmann Institute of Science has now revealed new details about the mechanisms controlling metastasis of breast cancer cells. Their findings, published recently online in Nature Cell Biology, add significantly to the understanding of metastasis and may aid, in the future, in the development of anti-cancer drugs. For any cell to migrate, it first must detach itself from neighboring cells and the intercellular material to which it is anchored. Before it can do this, it receives an order from outside the cell saying: "Prepare to move:' The Growth Factor This signal takes the form of a sub- stance called a growth factor which can activate a number of processes in the cell including division and dif- ferentiation. The growth factor attaches to a receptor on the cell wall, initiating a sequence of changes in the cellular structure. The cell's internal skeleton — an assembly of densely-packed pro- tein fibers — comes apart and the pro- tein fibers then form thin threads on the outside of the cell membrane that push the cell away from its neighbors. In addition, a number of protein levels change: some get produced in higher quantities and some in lower. To understand which proteins are modulated by the growth factor and the nature of the genetic mechanisms involved in cancer cell migration, a team of researchers pooled their knowledge and resources. The Weizmann team mapped all of the genetic changes that take place in the cell after the growth factor signal is received. As they sifted through the enormous amount of data, includ- ing details on every protein level that went up or down, one family of pro- teins stood out. Tensins, as they're are called, are proteins that stabilize the cell structure. But to the scientists' surprise, the amounts of one family member rose dramatically while, at the same time, the levels of another dropped. Despite the familial similarity, the team found a significant difference between them. The protein that drops off has two arms: One arm attaches to the protein fibers forming the skel- eton, and the other anchors itself to the cell membrane. This action is what stabilizes the cell's structure. The protein that increases, on the other hand, is made up of one short arm that only attaches to the anchor point on the cell membrane. Rather than structural support, this protein acts as a kind of plug, blocking the anchor point and allowing the skel- etal protein fibers to unravel into the threads that push the cells apart. The cell is then free to move, and, if it's a cancer cell, to metastasize to a new site in the body. In experiments with genetically engineered cells, the scientists showed that the growth factor directly influ- ences levels of both proteins and that these, in turn, control the cells' ability to migrate. Blocking production of the short tensin protein kept cells in their place, while overproduction of this protein plug increased their migration. Next, the scientists carried out tests on tumor samples taken from around 300 patients with inflammatory breast cancer, a rare but swift and deadly form of the disease, which is associ- ated with elevated growth factor levels. The scientists found a strong correla- tion between high growth factor activ- ity and levels of the "plug" protein. High levels of this protein, in turn, were associated with cancer metasta- sis to the lymph nodes — the first sta- tion of migrating cancer cells as they spread to other parts of the body. The Weizmann team believes the mechanism identified is clinically important. It can predict the develop- ment of metastasis and possibly how the cancer will respond to treatment. This discovery may, in the future, aid in the development of drugs to prevent or reduce the production of the unwanted protein, and prevent metas- tasis in breast or other cancers.