A Heterogeneous In Vitro Three Dimensional Model of Tumour-Stroma Interactions Regulating Sprouting Angiogenesis

摘要: Angiogenesis, the formation of new blood vessels, is an essential process for tumour progression and area significant therapeutic interest. Different in vitro systems more complex vivo have been described study angiogenesis. However, there are few human 3D to date which mimic cellular heterogeneity complexity angiogenesis within microenvironment. In this we describe Minitumour model – a 3 dimensional spheroid-based system consisting endothelial cells fibroblasts co-culture with breast cancer cell line MDA-MB-231, vitro. After implantation collagen-I gels, spheroids form quantifiable capillary-like structures. The pre-capillary sprouts supported by fibroblasts, act as mural cells, their growth increased presence cells. Characterisation using small molecule inhibitors inhibitory antibodies show that sprout dependent on factors cytokines known be important also shows response anti-angiogenic agents similar previously data. We demonstrate independent manipulation different types possible, common molecular techniques, before incorporation into model. This aspect spheroid analysis makes ideal high content studies gene function individual types, allowing dissection roles cell-cell interactions. Finally, technique, were able requirement metalloproteinase MT1-MMP but not sprouting