A team of cancer researchers at the Research Institute of the McGill University Health Centre (MUHC) at the Montreal Children's Hospital has discovered a new mechanism by which cancerous tumors stimulate the growth of the blood vessels that feed them, a process called angiogenesis. These findings may lead to new ways to control this process, which could translate into future therapies. Results were published February 20th in the online edition of the Proceedings of the National Academy of Sciences (PNAS).

Scientist have known that tumor cells can release "bubbles" called microvesicles containing various substances that allow the tumor to communicate with other tumor cells and with endothelial cells lining blood vessels, and stimulate changes in their behavior. In the new study, researchers identified microvesicles armed with the receptor for endothelial growth factor (EGFR), a key receptor tyrosine kinase involved in angiogenesis and tumor growth. Researchers used human squamous cell carcinoma cell lines to demonstrate the microvesicular transfer of EGFR from the tumor cells to endothelial cells.

They then showed that the endothelial cells that received the EGFR increased their production of vascular endothelial growth factor (VEGF), the primary stimulator of angiogenesis, and expression of VEGF-receptor-2 (VEGFR-2). Essentially, the microvesicle-derived EGFR re-wired the endothelial cells to express and respond to VEGF in an autocrine manner, a potentially important step in tumor angiogenesis.

"We had already demonstrated the existence of these vesicles as well as their importance in the communication process between cancer cells and their environment. But this new discovery is much more targeted and represents a new direction in terms of therapy," said study author Dr. Janusz Rak.

Notably, by blocking the microvesicle exchange using Diannexin, a derivative of annexin V, researchers inhibited both tumor growth and angiogenesis. "The molecule we used is effective both in vitro and in vivo. It prevents the formation of new blood vessels in mice with cancer and therefore strongly inhibits tumor growth," said Dr. Rak.

Diannexin blocked the in vitro fusion of vesicles and endothelial cells. In mice with cancer, Diannexin slowed blood vessel growth towards the tumor, resulting in anti-cancer effects. This finding is particularly important considering the treatment was applied in isolation without additional chemotherapy. If combined with other agents, this new way of treating cancer may be even more potent. Diannexin is also currently being developed as an antithrombotic medication.

By Roderick Smith, M.S.

References: PNAS published online before print February 20, 2009, doi:10.1073/pnas.0804543106