A novel experimental platform for investigating tumorigenesis and anti-cancer therapy in a human microenvironment derived from embryonic stem cells

Extract: There has been a growing awarenes in recent years that tumorigenesis properties are markedly affected by the surrounding tissue microenvironment at both primary and metastatic sites. Thus, it has been shown that tumor progression is associated with extensive remodeling of adjacent tissues to provide a supportive microenvironment for cancer cell proliferation, migration, invasion, and the formation of blood vessels required for supporting cancer growth. As an example, human prostate carcinoma-associated fibroblasts can promote tumorigenic transformation in initiated human prostate epithelial cells. Appreciation of the importance of the stromal response has led to the development of novel anti-cancer therapeutic agents targeted to frustrate stromal response factors, which support progressive tumor growth. Targets for investigation have included proteases, heparanase and other enzymes expressed by cancer cells or by adjacent stromal cells, which degrade extracellular matrix components and facilitate the release of cytokines and growth factors which stimulate angiogenesis, or support the growth and invasion of cancer cells. A great deal of attention has been directed at the development of anti-angiogenic molecules in particular, some of which have reached clinical trials.