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Low Density Lipoprotein Receptor Activity in Human Intracranial Tumors and Its Relation to the Cholesterol Requirement¹

Department of Clinical Pharmacology, Karolinska Hospital, S-104 01 Stockholm, Sweden [M. J. R., C. O. P.]; Metabolism Unit, Department of Medicine, Karolinska Institute at Huddinge University Hospital, S-141 86 Huddinge Sweden [B. A.]; and Ludwig Institute for Cancer Research, Stockholm Branch, Karolinska Institute, S-104 01 Stockholm, Sweden [V. P. C.]

The receptor binding of low density lipoprotein (LDL) was determined in homogenates of surgically removed specimens from primary and metastatic intracranial tumors and in some cases also from surrounding brain. Seventy-one specimens from 63 patients were analyzed. In a subsample of 16 specimens from 13 patients, the activity of 3-hydroxy-3-methylglutaryl-CoA reductase was assayed in parallel. The LDL binding in the tumors varied over a wide range. A significantly higher LDL binding activity was found when all tumor samples were compared to brain (P < 0.05). In the three patients where LDL receptor and 3-hydroxy-3-methylglutaryl-CoA reductase activities were assayed in both tumor tissue and surrounding brain, it was found that the receptor or the enzyme activity was increased in the tumors.

It is suggested that certain intracranial tumors have an increased cholesterol requirement and that this may be fulfilled by an enhanced LDL receptor activity or an increased 3-hydroxy-3-methylglutaryl-CoA reductase activity. The data indicate that the LDL receptor activity may be regulated independently of the reductase in intracranial tumors.

¹ This study was supported by grants from the Swedish Cancer Society, the Stockholm Cancer Society, the Swedish Society of Medicine, the Robert Lundberg Foundation, the Swedish Medical Research Council (Grants 14X-5964 and 03X-7137), and the King Gustaf V and Queen Victoria Foundation.

² Present address: Department of Molecular Genetics, University of Texas, 5223 Harry Hines Blvd., Dallas, TX 75235.

³ To whom request for reprints should be addressed, at Ludwig Institute for Cancer Research, Stockholm Branch, Box 60004, S-104 01 Stockholm, Sweden.

Received 5/12/88. Revised 9/11/89. Accepted 10/10/89.

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