Abstract B7: Annexin V inhibits local but not systemic murine fibrosarcoma growth by blocking phosphatidylserine

Abstract

Introduction: Phosphatidylserine (PS), a phospholipid expressed on the cytoplasmic surface of plasma membrane, becomes externalized during apoptosis and regulates immune activation. During our previous studies, we found that live tumor cells can express PS on the cell surface. We hypothesized that PS expression allows tumors to escape immune destruction, and blocking PS with annexin V (AnV) would retard tumor growth. Materials and methods: CMS5 fibrosarcoma tumor cells were engineered to secrete AnV. Balb/c mice were inoculated subcutaneously with 105-106 CMS5 cells. Tumor growth was determined. Data was analyzed using student t-test. Results: WT tumors grew significantly faster than AnV secreting tumors, with average size of 0.876 cm3 compared to 0.320 cm3 (p<0.05) in immune competent but not in SCID mice. To test whether AnV secreting tumors are intrinsically altered we inoculated mice with a mixture of 25% AnV secreting and 75% WT tumor cells. Growth of mixed cell tumors was identical to AnV secreting tumors, and was significantly smaller than WT tumors, 0.876 cm3 compared to 0.324 cm3 (p<0.05). To determine whether the effect of AnV was local or systemic mice were inoculated with tumor cells on each flank. Regardless of the type of tumor on the opposite side, WT tumors grew significantly faster than AnV secreting tumors with average size of .684 cm3 versus 0.345 cm3 (p<0.05). Conclusion: We demonstrated blocking tumor PS with AnV retards local tumor growth. The effects of AnV require an intact immune system. These findings suggest that PS promotes tumor tolerance and blocking PS with AnV may be used in future immunotherapy studies.