Advances in tumor angiogenesis Dendritic cells co-opted to the...( (Philadelphia PA) Researchers at the ...)

(Philadelphia, PA) Researchers at the University of Pennsylvania School of Medicine discovered that in ovarian cancer immune cells can change into blood-vessel cells, and eventually promote the life-sustaining vasculature of the tumor. These findings were initially observed in a mouse model of ovarian cancer that the investigators generated and then confirmed in human ovarian cancer. This work may lead to new approaches to fighting solid tumors.

George Coukos, MD, PhD, and his team, Jose Conejo-Garcia, MD, PhD, and Fabian Benencia, PhD, all investigators in the Abramson Cancer Center and the Center for Research in Women's Health and Reproduction, report their findings in this week's online publication and the September issue of Nature Medicine.

"These results clearly deal with ovarian cancer, but we think that the concept is applicable to solid tumors in general," says Coukos. Ovarian cancer is the leading killer among gynecologic cancers, causing about 25,000 new cases a year and about 15,000 deaths annually in the U.S. "One of the problems is that it's diagnosed late and we don't have effective treatments for it.

"Dendritic cells play a central role in the generation of antitumor immune response," says Coukos. "As a result, it was believed that these were mostly good players in inducing tumor rejection." But when dendritic cells are part of the tumor microenvironment, instead of stimulating an immune response, they deviate from the program and are co-opted into tumor angiogenesis. "When the dendritic cell precursors are put in the tumor context they form blood vessels that are functional," notes Conejo-Garcia. In a mouse model in which ovarian tumors expressed high amounts of the proteins beta-defensin and VEGF-A, dendritic cell precursors were attracted to the tumor, where they turned into an endothelial-like cell type. Endothelial cells are the cells forming the inner lining of blood vessels. They are critical for building tumor blood v
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
29-Aug-2004

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