BIOCHEMISTRY - DR. JAKUBOWSKI
Last Updated: 03/31/16
Learning Goals/Objectives for Chapter 5E: After class and this reading, students will be able to
The toxic effects of chemotherapeutic drugs might be eliminated if the drugs could be targeted to tumor cells and not to normal cells. Tumor cells presumably display unique protein molecules (tumor antigens) on their cell surface membranes that are not found on normal cell membranes. Drugs must enter the circulatory system of the specific targeted organ before they can be taken up by that organ. The endothelial cells that line the inner surface of blood vessels must display different proteins depending on the organ they are in, since circulating cells that interact with blood vessels in a specific organ appear to bind only to the endothelial cells in the specific organ. These cell and tissue-specific endothelial cell surface receptors impart specificity in binding. A recent study by Oh et al. demonstrated the presence of different proteins on endothelial cells found in blood vessels of normal mouse lungs and lung tumors. They injected silica particles into the blood. The particles bound to endothelial cells membranes. They homogenized, centrifuged and purified membrane-fractions bound to the silicon particles. The membranes were highly enriched in endothelial cells and caveolae, which are small indentations into the membrane and represent sites for the uptake of molecules, viruses, etc. into the cell. Molecular targets (such as viruses) could bind to receptors in the caveolae, and then through a process of invagination be taken up into the cell. The inner leaflet of the caveolae is lined with a protein called caveolin. Two endothelial cell transmembrane proteins, aminopeptidase P and annexin A1 were found specifically in normal and tumor lung endothelial cells, respectively. When given to rats with lung tumors, radioactive-labeled antibodies to annexin A1prolonged the life span of the rats.
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