Examining data on the genes HGF activates, the team found that the one specific gene, called jagged1, is among the most expressed. Jagged1 binds to a specific protein on the surface of the endothelial cells.

Wang speculated that if jagged1 is not secreted but found on the surface of tumor cells, then perhaps HGF gets jagged1 levels to increase, and that prompts a connection between the tumor and endothelial cells.

Sorting out this connection, Wang considered involvement of notch, another protein on the endothelial cells. Notch is known to help in the formation of blood cells, and jagged1 binds to notch.

Wang said he found it interesting that although much research has looked at cancer cells' secretion of proteins to form blood vessels, notch's function in cancer angiogenesis has not gotten the same attention. Notch, Wang said, pulls this whole complex operation together.

After this contact stimulates angiogenesis, the tumor gets nutrition and grows faster, Wang explained. Conversely, Wang hopes that blocking the signaling pathway can cut off the tumor's nutrition and stop its growth.

If this development pans out as a treatment, Wang said he envisions a two-pronged approach that attacks the protein secretion and the cell contact to kill cancer cells.

The next question Wang wants to explore is how these connections lead to metastasis, the spread of cancer throughout the body. He speculates that inflammation could trigger that pathway, and wants to look at the potential for controlling inflammation to stop tumor development.

"Head and neck cancer is under studied," Wang said. "The five-year survival rate hasn't improved in decades. We want to change that."

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Contact: Colleen Newvine
cnewvine@umich.edu
734-647-4411
University of Michigan
18-Jul-2005