The study centers on capillary formation, or angiogenesis, a proce shown to be e ential to tumor progre ion as tumors attract capillaries to provide oxygen e ential for growth and frequently use those same ve els to send out metastatic cells. By zeroing in on these capillary-forming protei , drug researchers may be able to treat a tumor by directly cutting off its blood su ly.
Drug researchers, using tools available since the human genome was sequenced, seek ecific targets to develop more precise cancer drugs with fewer side effects. \"Once you have a unique target,\" explained biologist Diane Rodi, \"you don\'t have the side effects of the drugs – most cancer drugs are anti-growth drugs that kill all the growing cells in the body. Most cancer therapies are not very ecific and that is why they are so toxic.\"
The Argo e biologists identified 217 protei involved only in capillary formation -- morphogenesis -- by finding all the gene products turned on during capillary formation and subtracting out those related only to growth, or proliferation, in a novel proce called subtractive tra criptomics.
Argo e biologists grew human endothelial cells – the cells involved in blood ve el formation – on a tumor ti ue-mimicking plate. As the capillaries grew over an 8-hour period, researchers isolated RNA samples at intervals – at 30 minutes, 1 hour, 2 hours, 4 hours and 8 hours. To determine which genes do not contribute ecifically to blood ve el formation, endothelial cells were grown on gelatin-coated plastic. RNA was isolated at the same intervals as on the tumor ti ue-mimicking plate.
Each RNA sample was tested using microarray analysis at the University of Chicago. The microarrays hold 44,000 samples of known RNA coded by the human genome. A reaction reveals the RNA that is being produced at each stage of the biological proce . RNA codes for protei .
\"We wanted to find the protei that are only made when the endothelial cells are making a capillary, not when they are just growing,\" Rodi said. \"We took all of the genes that were made on the ti ue plate and subtracted out those from the plastic plate. And we were left with 217.\"
The researchers sought the protei in the capillaries using commercially available antibodies. Of the 16 morphogenesis- ecific protei tested, all were found in the capillaries after they were completely formed.
The capillary research revealed a bonus i ight into a still m