As cancer cells migrate in the body from a primary tumor, they’re chaperoned by clumps of platelets. These bloodstream particles shield the cells from damage and help them invade new tissues in the process called metastasis. Researchers have now discovered how one molecule helps tumor cells aggregate their platelet entourages.
Researchers had known that podoplanin, a protein found on the surface of many tumor cells, was involved in metastasis. But no one had found receptors for the protein on the surfaces of platelet cells, so it wasn’t clear how podoplanin worked.
Katsue Suzuki-Inoue of the University of Yamanashi in Japan and her colleagues noticed a similarity between the way in which a snake toxin, rhodocytin, and podoplanin activate platelets. Activation promotes clumping and also triggers platelets to release a variety of cellular factors that can contribute to the growth of blood vessels feeding metastatic tumors.
In chemical tests and assays of tumor cells, the researchers showed that podoplanin interacts with the CLEC-2 receptor, the same receptor by which rhodocytin activates platelets. The podoplanin-receptor interaction thus appears both to protect tumor cells as they move in the bloodstream and to contribute to their growth, Suzuki-Inoue says. The team’s findings appear in the Sept. 7 Journal of Biological Chemistry.
The new findings supply only a piece of the tumor-metastasis puzzle, she adds. But targeting the podoplanin–CLEC-2 interaction could be a strategy for new antimetastasis drugs. Suzuki-Inoue and her team are now examining how the two substances come together on the cell surfaces.