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CONTACT: JENNIFER CRONIN
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e-mail: jennifer-cronin@uiowa.edu

Release: Sept. 2, 1999

UI researchers discover aggressive cancer cells may make own blood vessels

EDITOR'S NOTE: Background video, including interviews with researchers, is available upon request. Please contact Tom Moore at (319) 356-3945.

IOWA CITY, Iowa — Until now, researchers widely assumed that tumors attracted nearby blood vessels to provide tumors with nutrition and pathways for tumor cells to spread throughout the body. This hypothesis, known as tumor angiogenesis, is the basis of intensive investigation and clinical trials worldwide.

However, in a study published in the September issue of the American Journal of Pathology, a University of Iowa research team reports that highly aggressive cancer cells themselves may generate their own vascular networks independent of angiogenesis. Because the researchers' discoveries call attention to an alternative pathway that is responsible for aggressive tumor growth and spread, the findings potentially could change the way cancers are regarded, diagnosed and treated.

The UI investigation was conducted by Andrew J. Maniotis, Ph.D., assistant research scientist in anatomy and cell biology; Robert Folberg, M.D., UI professor of pathology and ophthalmology; and Mary J.C. Hendrix, Ph.D., UI professor and head of anatomy and cell biology, and deputy director of the UI Cancer Center; together with their colleagues.

The researchers discovered that as human cancer cells progress toward more deadly forms, groups of aggressive cancer cells build primitive vascular channels. The researchers found this to be true in both specially engineered cultures and human cancer specimens.

The results may explain why aggressive cancers do not respond to conventional chemotherapies or why tumor growth and spread can continue even when conventional therapies are combined with experimental chemotherapies that may block angiogenesis in animal models and in humans.

"The vascular channels form between tightly packed groups of aggressive cells; and basic tissue processes, such as perfusion, can continue to operate within the tumor even though more complexly orchestrated processes are shut off by drugs or by the tumor itself as it grows," Maniotis said. "In addition, because these vascular channels can be constructed in the laboratory with human cells, new forms of cancer therapy could be developed that would specifically interfere with the way tumor cells pack together to form these channels."

Both before and after aggressive cancer cells spread, the vascular channels form characteristic patterns in human cancer patients that resemble those that are seen only in early embryos, Hendrix said.

Folberg added, "Because these patterns can be identified through angiographs or by specialized ultrasound, it may be possible to develop new non-invasive imaging tests to detect aggressive cancers. These tests may complement and perhaps even substitute for some forms of invasive biopsies."

Although the UI researchers focused their attention on ocular and skin melanoma, they have preliminary data suggesting that this phenomenon may occur in other tumors. The researchers are awaiting scientific peer review before they release any additional information.

Because this study deals with new and novel concepts in cancer biology, the American Journal of Pathology article is accompanied by a commentary by Mina Bissell, a noted breast cancer researcher and Life Sciences Division director at the Lawrence Berkeley National Laboratory. The journal Science also plans to include a story on the UI findings in its Sept. 3 issue.

In addition to Hendrix and Maniotis, the other researchers from Hendrix's lab who were involved in this study included Angela Hess, UI graduate student, and Elisabeth Seftor, research specialist. Folberg's research assistant Lynn Gardner also contributed to this investigation, as did Jacob Pe'er from the Hadassah University Hospital, and Jeffrey M. Trent and Paul S. Meltzer from the National Institutes of Health (NIH), Human Genome Research Institute.

The research was made possible through support from the UI Central Microscopy Research Facility and the Charles Hendrix Research Foundation, and through grants from the National Eye Institute and the National Cancer Institute, as well as a grant from Research to Prevent Blindness Inc., for which Folberg serves as a senior scientific investigator.

More information about the UI research is available at the following Web sites: http://webeye.ophth.uiowa.edu/eyepath/ and http://www.uiowa.edu/~anatomy/pages/labs/hendrix.html