Fig. 1.

The progression of the canceration through angiogenesis. The rapid expansion of tumor results in a reduction in the oxygen supply. The consequent hypoxic tumor microenvironment stimulates excessive angiogenesis via increasing various angiogenic pro-factors including VEGF, PDGF, FGF, and angiopoietin. Later, new blood vessels facilitate the transportation of oxygen and nutrients to further support the survival, growth and proliferation of tumor cells. When tumor cells develop a more aggressive phenotype, they continue to proliferate, spread and induce angiogenesis, with the invasion and metastasis of tumor cells into distant tissues through blood circulation