Molecular targets in antimetastatic therapy of gastrointestinal tumors

For the control of gastrointestinal tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of tumor cells was compared in a Boyden chamber and in an extracellular matrix based three-dimensional cell culture (3-DCC) model system. The Boyden chamber offers a model of single tumor cell migration, whereas the 3-DCC model system demonstrates invasive growth in the form of a cluster. Our study provided evidence that certain cytotoxic/cytostatic agents at appropriate concentrations were able to preferentially inhibit certain types of migration relative to cell proliferation. Single cell migration was selectively inhibited by taxol at very low subtoxic concentration, whereas 5-hexyl-2'-deoxyuridine (HUdR) exclusively inhibited the cluster type of migration. The borrelidin compound was able to inhibit both types of tumor cell migration, but single tumor cell migration was much less affected. Taxol is recommended as an agent acting against single cell migration, as well as HUdR and borrelidin as leading compounds for developing antimetastatic drugs against cluster type migration. The combination of these drugs offers a possibility of acting against both single cell and cluster type tumor cell migration.