Combined with previous findings that the protein is depleted or missing in a majority of metastatic human cancers, the findings suggest that fibulin-5 may one day be an effective cancer therapy. William Schiemann, Ph.D., Assistant Professor in the Program in Cell Biology at National Jewish, and postdoctoral fellow Allan R. Albig reported their findings in the June issue of DNA and Cell Biology.
"We believe fibulin-5 shows real promise as a cancer therapy," said Schiemann. "When we slightly altered the naturally occurring protein it was even more effective at inhibiting the sprouting of new blood vessels."
Cancer tumors need nutrients and oxygen supplied by blood vessels in order to grow. They also use blood vessels to spread to other parts of the body.
This process, known as metastasis, is the most lethal characteristic of cancer and the leading cause of cancer-related death. The strategy of fighting cancer by preventing the growth of new blood vessels has generated great interest in recent years, with the first antiangiogenic drug being approved earlier this year.
Endothelial cells have been the target of most antiangiogenic strategies. Endothelial cells are specialized cells that develop into blood vessels. Fibulin-5, a member of a family of extracellular matrix proteins that regulate tissue development, remodeling and repair, interacts with endothelial cells.
In cell culture studies, Schiemann and Albig showed fibulin-5 levels drop significantly when endothelial cells begin to form blood vessels, a process known as tubulation. They also show that high levels of fibulin-5 could prevent the sprouting of new blood vessels by inhibiting the proliferation and movement of endothelial cells.
Fibulin-5 interfered with signaling by the proangiogenic factor VEGF, and increased level
Contact: William Allstetter
National Jewish Medical and Research Center