Fragmin/Protamine Microparticles (F/P MPs) as Cell Carriers Enhance the Formation and Growth of Tumors In Vivo

Abstract

Mixing a low-molecular-weight heparin (e.g., fragmin) with protamine results in the formation of water-insoluble fragmin/protamine microparticles (F/P MPs) approximately 0.5–3 μm in diameter. In this study, we investigated the ability of F/P MPs to improve the viability of Lewis lung (3LL) cancer cells, B16 (B16) melanoma cells, and a human hepatoma (Huh7) cell line in a suspension culture, and the ability of F/P MPs to enhance tumor take rate and growth in vivo. F/P MPs rapidly bound to the surface of the cells. The interaction of the cells with F/P MPs induced formations of the tumor cell/F/P MP aggregates and maintained the viability of those cells in suspension for at least 3 days. The addition of F/P MPs with FGF-2 significantly enhanced the growth rate of the cells in a fetal bovine serum (FBS)-free medium. The tumor cell/F/P MP aggregates, which were subcutaneously injected into the backs of mice, significantly stimulated the formation and growth of subcutaneous tumors consisting of 3LL, B16, and Huh7 cells. Furthermore, the tumors produced by injection of 7.5 × 105 Huh7 into nude mice did grow only with F/P MPs. Thus F/P MPs can utilize as cell carrier for tumor cell transplantation.