Clotting Factor Plays Critical Roll in Tumor Angiogenesis

A variant form of the blood clotting protein "Tissue Factor" or TF has been identified as a key modulator of angiogenesis, and may serve as a target for chemotherapy aimed at denying tumors the increased blood supply they require for growth and metastasis.

Investigators at the University of Cincinnati (OH, USA) in collaboration with colleagues at Leiden University (The Netherlands) worked with a modified form of TF known as alternatively spliced Tissue Factor or asTF, which previously had been found to be present in high levels in specimens of human cervical cancer.

They reported in the October 29, 2009, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS) that the molecular activity of asTF differed substantially from that of native TF. The modified TF was shown to bind to surface molecules called integrins on endothelial cells, which induced signaling cascades that triggered angiogenesis. Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and thereby define cellular shape, mobility, and regulate the cell cycle. Increased interaction between asTF and integrins resulted in increased cell adhesion, cell migration, and development of new blood vessels in both cellular and animal models.

"This is an important breakthrough in cancer research because we are able to draw a more complete molecular picture of how Tissue Factor contributes to cancer growth," explained contributing author Dr. Vladamir Bogdanov, professor of hematology at the University of Cincinnati. "This will help translate basic research into real-life for therapies targeted to stop angiogenesis."

"Our findings introduce a whole new way of studying how the Tissue Factor gene influences tissue formation process, including angiogenesis," said Dr. Bogdanov. "This is another level of understanding the molecular actions behind Tissue Factor."

The investigators anticipate that these studies will encourage development of new ways to target specific forms of Tissue Factor to stop cancerous cell growth while causing minimal impact on the body's capability to stop bleeding.

Related Links:
University of Cincinnati
Leiden University