O-Alkyl Lipids in Surface Membranes of Tumor Cells

Friedberg, Samuel

Abstract

Neoplasms contain increased quantities of O-alkyl lipids. In order to detect surface membrane abnormalities which might exist in malignant versus non-malignant tumors, we have measured the O-alkyl lipid content of these structures. The surface membrane O-alkyl lipids of a series of transplantable metastasizing and non-metastasizing rat tumors was quantitated by photodensitometry. The results suggest that more rapidly growing and more malignant neoplasms contain greater quantities of O-alkyl phospholipids than less aggressive tumors. We are currently conducting a similar evaluation of a series of human mammary tumors obtained as surgical specimens and analyzed for estrogen and progesterone receptors. We are attempting to correlate the degree of malignancy of these tumors with their ether lipid content and with their concentrations of estrogen and progesterone receptors. An additional project in progress is an attempt to purify O-alkyl synthase, the enzyme responsible for the synthesis of O-alkyl dihydroxyacetone-phosphate. Although a method for purifying this enzyme has been recently published, we are taking a somewhat different approach involving novel forms of chromatography. Preliminary studies in this area involve isolation of this enzyme from Tetrahymena pyriformis. If successful, the procedure developed will be used on the enzyme found in tumors. In addition to the above, we are continuing work on the mechanism of action of O-alkyl synthase. In the past year, we have conducted experiments confirming the basic validity of our proposed mechanism and confirmed the work of others that the action may be, in part, reversible. We are also studying the stoichiometry involved in that aspect of the mechanism involving a hydrogen exchange and the release of fatty acid from acyl-dihydroxyacetonephosphate. Preliminary data suggest that the release of one proton is accompanied by the release of one fatty acid which retains both carboxyl oxygens. This unusual form of ester cleavage was recently demonstrated in this laboratory. The results have broader implications with regard to the mechanism of action of a related enzyme that may function via a similar mechanism, namely, the acylhydrolase which cleaves acyl-dihydroxyacetonephosphate. (A)