A Swiss-based research team has published a new mechanistic description of how tumor cells migrate to the lymphatic system in the early stages of tumor metastasis. This new understanding holds significant potential for developing anti-metastasis therapies.
Scientists know that tumor cells spread via the lymphatic system, but they dont understand the details of how this deadly migration takes place. In the June 2007 issue of the journal Cancer Cell, EPFL Professor Melody Swartz and postdoctoral researcher Jacqueline Shields provide an explanation along with data to support it.
Tumors produce excess fluid that continually percolates from the tumor towards nearby lymphatic vessels. The EPFL research shows how tumor cells use a clever chemical strategy to exploit this slow, one-way flow in order to migrate to functional lymphatic vessels.
As part of their intercellular drainage job, lymphatic tissues secrete small quantities of a signaling molecule. Cells migrate towards high concentrations of this molecule, so if they are close enough to the lymphatic to sense the molecule, they will migrate towards the vessel. Swartzs group showed that tumor cells secrete this same molecule. Since lymphatics drain fluid, there will always be slow fluid flow going away from the tumor into the lymphatic vessel. This slow flow biases the concentration distribution of this molecule towards the lymphatic, and the tumor cell follows it, like the proverbial carrot on a stick. Near the vessel, concentrations of the signaling molecule are reinforced by the lymphatics own secretions, fine tuning the tumor cells migration and guaranteeing that they will home in on the lymphatic.
To demonstrate this new concept, the researchers engineered a tissue culture model of the tumor-lymphatic microenvironment and developed computational models to calculate the gradients of the signaling molecule.