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 waterinsoluble fragmin/protamine microparticles (F/P MPs) approximately 0.5-3 lm 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 9 10 5 Huh7 into nude mice did grow only with F/P MPs. Thus F/P MPs can utilize as cell carrier for tumor cell transplantation.

Novel Experimental and Clinical Therapeutic Uses of Low-Molecular-Weight Heparin/Protamine Microparticles

“…LMW-H/P MPs also bind to the surface of various adhesive tumor cells, promoting cell-to-cell interaction and increase cellular aggregation with the LMW-H/P MPs. The tumor cells/LMW-H/P MPs-aggregates substantially promote cell survival and proliferation of those tumor cells in vitro , and reliably induce tumor formation and rapid tumor growth in vivo [ 26 ]. Taken together, LMW-H/P MPs constitute a new convenient and effective biomaterial that function as a tumor cell carrier in vivo .…”

“…The LMW-H/P MPs generate a stable paste-like coating through complete drying. It is probable that polypeptides, such as FGF-2, interleukin (IL)-3 and granulocyte/macrophage-colony stimulating factor (GM-CSF), once bound to the LMW-H/P MPs-coated plates, are gradually released from the coated surface in vitro with a half-life of 4–6 days [ 26 ]. Furthermore, LMW-H/P MPs-coating could optimally stimulate growth of hMVECs and hDFCs in low FBS (1%)-DMEM with FGF-2 and growth of hematopoietic cell line (TF-1) with IL-3 and GM-CSF ( Figure 7 ) [ 26 ].…”

“…LMW-H/P MPs also bound to the surface of tumor cells (e.g., Lewis lung cancer cells (3LL), B16 melanoma cells (B16), and a human hepatoma cell line (Huh7)), promoting the aggregation of the tumor cells with the LMW-H/P MPs and increasing cell-to-cell interactions. The tumor cells/LMW-H/P MPs-aggregates substantially promoted tumor cell viability and proliferation in vitro , and reliably induced rapid tumor formation and tumor growth in vivo [ 26 ].…”

Augmented Pentose Phosphate Pathway Plays Critical Roles in Colorectal Carcinomas

“…In order to prevent bacterial or fungal contamination, the medium was replaced with fresh medium 24 h after cell preparation. After 3 more days of culture, both attached and floating spheroids were collected, mixed with extracellular scaffold [14] and injected into nude mice subcutaneously. We did not adjust the cell number precisely at the first transplantation, since the ratio between attached and spheroid cells varied individually.…”

Biomedical Application of Low Molecular Weight Heparin/Protamine Nano/Micro Particles as Cell- and Growth Factor-Carriers and Coating Matrix

“…Those results indicated that LMWH/P N/MPs constitute an effective biomaterial that functions as a tumor cell carrier in vivo . The application of LMWH/P N/MPs as a tumor cell carrier offers a more reliable model in both allograft and xenograft transplantation for cancer research [ 45 , 46 ].…”