Abstract
Purpose/Objective: The prognosis of patients with glioblastoma multiforme (GBM) is poor despite aggressive multimodality treatment. Recent approaches to improve this situation include ligand-receptor targeting, which may facilitate the delivery of isotopes, toxins or radiosensitizing drugs directly into tumor cells. Tumor growth is associated with high turnover of cell cholesterol, and to sustain adequate cholesterol levels, many cells take up plasma low-density lipoprotein (LDL), the main cholesterol carrier in blood. This process involves receptor-mediated endocytosis through the LDL receptor (LDLR). Because some tumors are known to require high amounts of LDL, it has been suggested that LDL might serve as a selective vehicle for intracellular delivery of therapeutic compounds. Human GBM lines in culture have variable amounts of LDLR, and it was shown that this receptor mediated the endocytosis of a boronated protoporphyrin into the cells. Based on this information as well as experimental data showing LDLR levels to be relatively low in neurons and glia, we hypothesize that LDLR may be a unique receptor to use for targeted delivery of cytotoxic agents into brain tumors. The current study was carried out to determine the extent of LDL receptor expression in human GBM.
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