Sept. 19, 2007
UI biology researchers receive over $800,000 in grants for tumor cell study
The laboratory of Christopher Stipp, assistant professor in the University of Iowa College of Liberal Arts and Sciences Department of Biological Sciences, recently received two grants totaling more than $800,000 to study how tumor cells migrate.
The first grant is a four-year, $703,000 grant from the American Cancer Society, while the second is an 18-month, $110,610 grant from the U.S. Department of Defense.
The two grants will expand on a separate but related research project funded by a three-year, $349,825 grant received in 2006 from the Roy J. Carver Charitable Trust to study how cells regulate the choice between belonging to cohesive groups or striking out on their own -- an aspect of cell behavior that plays an important role both in normal cell development and in tumor cell progression.
The research funded by the American Cancer Society is aimed at gaining a better understanding of the mechanisms of tumor cell migration, or metastasis. During metastasis, Stipp says, tumor cells complete multiple steps in order to move. At each step, they make new adhesive contacts at the front edges of the cells and also release adhesive contacts at the trailing edges. The project focuses on how these processes are controlled, he says.
In order to migrate, tumor cells use protein molecules on their cell surfaces called integrins. Significantly, normal cells also rely on integrins to move throughout the body. As a result, some drugs targeting integrins have been successful in some clinical settings, but have caused dangerous side effects in others, he says.
The UI research project investigates a novel integrin control mechanism that might be co-opted to inhibit motility without grossly disrupting integrin function in normal cells, says Stipp. Understanding the key features of this novel control mechanism may lead to new strategies for curtailing integrin-dependent tumor cell metastasis without harming the ability of normal cells to use integrins, he adds.
Similarly, the Department of Defense grant is aimed at developing new strategies for inhibiting the adhesive interactions of prostate carcinoma cells with molecules located in the spaces outside the cell that provide a substrate supporting metastasis, Stipp says.
"During prostate cancer metastasis, tumor cells use integrins to migrate and invade. Our objective is to investigate new ways to inhibit integrins that may allow us block their function in tumor cells without causing unacceptable side effects in normal tissues," he says. Interestingly, integrins have the ability to assume multiple shapes so that inactive integrins are bent over and facing back toward the cell surface, while active integrins are straight and extend away from the cell, where they can bind to proteins in the space outside the cell. On any given cell and at any point in time, some of the thousands of integrin molecules may be inactive and others may be active.
"If we could develop strategies to shift the ratio of active to inactive integrins on the cell surface, it would be like having a dimmer switch instead of an on-off switch," Stipp says. "It might allow us to turn down integrin function enough to inhibit tumor cell migration, but not so much that integrin function in normal tissues is dangerously impaired."
On the subject of his research environment, Stipp says: "The research that made these grants possible is truly a lab effort, and I feel privileged to be able to work with such a talented group of young researchers. In addition, the work also relies on a key collaboration with my colleague, Professor Michael Henry, at the UI Roy J. and Lucille A. Carver College of Medicine Department of Molecular Physiology and Biophysics. Between the main campus and the medical school, there are so many great research groups here at the UI that it's a very exciting place to do science. That's why, when I was offered the opportunity to start my lab here four years ago, I jumped at the chance."
STORY SOURCE: University of Iowa News Services, 300 Plaza Centre One, Suite 371, Iowa City, Iowa 52242-2500