In 2000, another set of investigators came across a protein on the surface of platelets and dubbed it C-type lectin-like receptor 2, or CLEC-2.
After six years of research and collaborations with British investigators, the team in 2006 discovered how rhodocytin-a molecule purified from the venom of the Southeast Asia pit viper Calloselasma rhodastoma-binds to the CLEC-2 receptor protein on the platelet surface, spurring the platelet to clot with others like it.
Then, in 2007, the researchers reported how a separate molecule, called podoplanin, binds to the CLEC-2 platelet receptor protein very much like the venom molecule does.
Using a mouse model, the team in 2008 showed that blocking the tumour protein podoplanin from binding with the platelet receptor protein CLEC-2 could prevent tumours from metastasizing to the lung.
The recent investigations hinged on the generation and study of genetically engineered mouse embryos that lacked the platelet receptor protein CLEC-2.
In the end, the experiments showed that CLEC-2 is not only necessary for blood clotting but also necessary for the development of a different type of vessel, specifically lymphatic vessels that carry fluid away from tissues and prevent swelling, or edema.
"During fetal development, the CLEC-2 deficiency disturbed the normal process of blood clotting and, in fact, the normal development and differentiation of blood and lymphatic vessels.
"These findings suggest that the interaction between CLEC-2 and podoplanin in lymphatic vessels is necessary for the separation between blood vessels and lymphatic vessels," added Hirashima.
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.