Fondation Latsis Internationale Award 2007 - Shields Jacqueline

"For her fundamental research in cancer metastasis, specifically for demonstrating the novel mechanism of autologous chemotaxis for cell migration into lymphatic vessels"

Autologous chemotaxis: a novel mechanism to explain how tumor cells find lymphatics.

Tumor metastasis is the major cause of cancer related deaths. Many tumors hijack the lymphatic system to spread, but how tumors find lymphatics is unclear. Tumors contain leaky blood vessels that exude fluid which is collected by surrounding lymphatic vessels and results in slow, one way fluid flow always from the tumor towards lymphatics. Using a unique tissue-engineered model designed to recreate the tumor microenvironment, we have shown that tumor cells migrate specifically towards functional lymphatics because of this slow flow.

We show that flow biases the distribution and concentration of tumor derived signals towards the lymphatic causing the tumor cell to follow, and once near a vessel, the lymphatics own signal further fine tune the tumor cells' homing into it. Significantly, we demonstrated i) that tumor cells respond and migrate towards a biochemical signal whilst at the same time being the of the cue and ii) the significance of the biophysical environment when studying biological phenomenon.Understanding such a fundamental mechanism holds potential for new anti-metastasis therapies; by preventing a cell from signaling to itself or even disrupting lymphatics so the tumor cell does not "know" in which direction to migrate, tumors could be prevented from finding lymphatics and spreading.