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Human Glioblastoma Cell Lines: Levels of Low-Density Lipoprotein Receptor and Low-Density Lipoprotein Receptor-related Protein¹

Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 [L. M., E. A. B., K. A. B., L. J. K., T. M. F.], and Brain Tumor Research Center, University of California, San Francisco, California 94143 [D. F. D.]

The status of the low-density lipoprotein (LDL) receptor and LDL receptor-related protein (LRP) in seven human glioma cell lines was evaluated to extend our knowledge of human glioblastoma multiforme tumor metabolism for future drug design. Cell lines SF-767, SF-763, A-172, U-87 MG, U-251 MG, U-343 MG, and SF-539 were used. Binding of ¹²⁵I-labeled LDL to these cells at 4°C was carried out to determine the number of LDL receptors on cells and the affinity of LDL for these receptors. The content of LRP was measured by immunoblotting. The presence of specific saturable LDL receptors was proven in six of the cell lines investigated. SF-767 cells revealed high-affinity LDL binding (equilibrium dissociation constant, K_d = 7 nM) and maximum binding capacity approximating 300,000 receptors/cell. Most of the remaining cell lines had relatively lower affinity (K_d = 38–62 nM) but also had very high numbers of receptors (128,000–950,000/cell). All cell lines exhibited LRP, but the expression was variable. The cell lines SF-539, U-87 MG, and U-343 MG were particularly rich in this protein. The data suggest that glioblastoma cells have high numbers of LDL receptors; however, there is considerable variation in binding affinity. Overall, this finding suggests that LDL receptors on glioblastoma cells could potentially be useful for targeting antitumor agents. LRP, a multifunctional receptor expressed on glioblastoma cells, also has the possibility for serving as a therapeutic target.

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