The Effects of Heparinoids On An EL4 Ascites Lymphoma As Mediated By Basic Fibroblast Growth Factor In Vivo Using A C57BL/10 Mouse System and In Vitro Using Murine Cell Lines
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Neoplasms are capable of independently reaching a maximum tumor diameters of 1- 2mm. To expand beyond this, neoplasms require a vascularised tumor stroma. Fibroblasts play a pivotal role in the development of tumor stroma. Basic Fibroblast Growth Factor (bFGF) is a mitogen for fibroblasts and forms complexes with heparinoids such as xylan (pentosan sulfate) and heparin itself which are thought to prevent the action of bFGF. The aims of this project were to use immunoperoxidase staining to investigate the presence and effects of bFGF in cell cultures of EL4 lymphoma cells and in subcutaneous murine tissue at various stages after transplantation of an EL4 lymphoma. In vitro investigations into the effects of heparin and xylan on EL4-induced fibroblast proliferation were intended to determine the therapeutic anti-tumor potential of these heparinoids. The investigation found that bFGF was contained within EL4 cells, and released from storage in the ECM as the tumor developed. DMEM and EL4 conditioned medium caused a 260% increase in cellular density of cultured mouse embryo fibroblasts (MEF) over the cellular density of MEF conditioned with DMEMFCS alone, indicating the presence of a fibroblast mitogen such as bFGF in EL4 exudate. Heparin appeared to have a limited anti-proliferative effect on MEF grown in the presence of EL4 conditioned medium, whereas the cellular density of MEF grown in the presence of EL4 conditioned medium and xylan (50 µg/ml) was 46% of the cellular density of MEF grown in EL4 conditioned medium without xylan. Xylan therefore appears to have substantial potential as an anti-tumor agent targeted specifically at inhibiting the role of bFGF in the development of tumor stroma.