Regulation of membrane function by lipids; implications for tumor development.

Abstract

Increase in the lipid fluidity of membranes increases the turnover number of each diffusible unit, but in general decreases its accessibility to ligand binding. As a result, many membranal functions reach a maximal activity at a specific lipid fluidity. These effects of membrane fluidity bear direct implications on tumor development with significant clinical potential. Two main avenues, by which lipid manipulation could be applied in cancer treatment are now being studied in experimental animals and cancer patients. In the first, the immunogenicity of tumor cells in syngeneic and autologous systems increase upon increase of the membrane microviscosity which is in line with the findings that membrane antigens become more exposed upon such treatment. Irradiated tumor cells with increased membrane microviscosity (e.g. by incorporation of cholesteryl hemisuccinate, CHS) thus act as strong and specific vaccine against the viable untreated tumor cells of the same kind. The second lipid manipulation relates to restoration of suppressed immune competence. A special mixture of lipids (Active Lipid, AL) designed to efficiently fluidize cell membranes was found to restore various immunological functions of leukocytes from cancer patients. The combination of augmentation of tumor immunogenicity and restoration of immune functions by such lipid manipulations is expected to constitute an innocuous active immunotherapy regimen for cancer treatment.