CHAMPAIGN, Ill. - Biologists striving to understand the mechanisms of cell migration have gained new insight by gaining control of - and even applying the brakes to -- cell movement by altering a calcium-regulated traffic signal that dictates how cells stick to their environment.
Learning about the basic mechanisms of how cells move may have implications for a wide range of diseases, including inflammatory problems such as arthritis and asthma as well as cancer invasion and metastasis, said Anna Huttenlocher, an assistant professor of pediatrics in the University of Illinois College of Medicine at Urbana-Champaign and an affiliate in the department of cell and structural biology.
U. of I. researchers have been looking at the relationship of integrin receptors, which are protein molecules that link the outside and inside of cells, with cell movement. They play a pivotal role in cell adhesion. A cell moves when the front protrudes and sticks to something else. The rest of the cell follows as it contracts and slinks forward -- if the tail decides to go along.
In December's Journal of Biological Chemistry, Huttenlocher and colleagues described how an inhibitor of a calcium-dependent protease (an enzyme) called calpain inhibits cell movement. Studies of live cells by time-lapse videomicroscopy showed that the inhibitors tightened adhesion properties in hamster ovarian cells and thwarted the tail's ability to let go. Previous research had found higher calcium levels at the rear of a cell, suggesting a possible regulatory role.
In a paper accepted for publication in the Journal of Cell Biology, researchers also found that, depending on the type of integrins present on the surface of cells, cells can either move apart easily or become stuck to each other. Under time-lapse videomicroscopy, the researchers were able to see how cell movement totally shut down when a specific receptor was expressed.
"One of the ways in which this is important is when you think of tumor cell biology," Huttenlocher said. "A tumor should not be able to invade and metastasize if the individual cells can't move away from each other."
In addition to gaining the ability to stop cell migration, understanding the basic mechanisms could be used, for example, to make desirable cells get into wounds to promote healing, she said.
The December paper was written by Huttenlocher and Alan F. Horwitz, head of the U. of I. department of cell and structural biology; Sean P. Palecek, a Whitaker Foundation Graduate Fellow in Biomedical Engineering at the Massachusetts Institute of Technology; Qui Lu, Wenzli Zhang and Ronald L. Mellgren of the Medical College of Ohio, Toledo; Douglas A. Lauffenburger of the Center for Biomedical Engineering at MIT; and Mark H. Gingsberg of the Scripps Research Institute, La Jolla, Calif. The work was funded by the National Institutes of Health and the Arthritis Foundation.
The Cell Biology paper was written by Huttenlocher, Horwitz and U. of I. graduate students.
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