Abstract P1-02-04: The Influence of Matriptase-2 on Angiogenesis and Tumour Growth In Vivo.

Abstract

Abstract Background: Metastasis is a key part of cancer progression and angiogenesis plays a large role in the ability of cancer cells to spread around the body and in the progressive growth of the primary tumour. Matriptase-2 is a cell surface serine protease believed to have implications in cancer metastasis. The current study aims to assess the importance of matriptase-2 in angiogenesis and tumour growth, using in vitro and in vivo models. Methods: Matriptase-2 was over-expressed in the HECV endothelial cell line, previously displaying minimal matriptase-2 expression, through the transfection of a mammalian expression construct containing the full coding sequence for matriptase-2. Following verification of forced expression, the cellular effects of matriptase-2 were examined using a number of in vitro cell models. The effect of matriptase-2 over-expression was also examined in in vivo mouse models by co-delivery of endothelial cells and tumour cells. Results: Matriptase-2 significantly reduced the motility (46.47±16.18 vs 10.93±2.80 p=<0.01) of the HECV cells and their ability to form tubule structures (23841.60±744.75 vs 9817.80±933.85 p=0.01) in an in vitro angiogenesis Matrigel tubule formation model. Matriptase-2 was found to have no significant effect on the growth (691.52±100.17 vs 763.50±91.43 p=0.110) and cell-matrix adhesion of the HECV cells (64.20±8.70 vs 57.42±4.50 p=0.530). However, the in vivo studies showed a reduction in tumour growth and development following co-injection of cancer cells with endothelial cells over-expressing matriptase-2 compared to co-injection with control endothelial cells. The sizes of tumours in two tumour models were: 70.99±19.52mm3 for tumour cells with control endothelial cells vs 0.17±0.10 mm3 for tumours with Matriptase-2 over-expression endothelial cells, p=<0.01; and 80.41±18.31 mm3 vs 43.12±20.33 mm3 p=0.08, in the other tumour model. Conclusion: Matriptase-2 appears to negatively influence angiogenesis through its inhibitory effect on endothelial cell motility and tubule formation. This is corroborated by the reduction of tumour growth, in vivo. Together this data suggests that matriptase-2 has an important role in the control of angiogenesis and tumour development. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-04.