Fig. 2
The role of neo-angiogenesis for tumor metastasis from local to distant sites. (1) The local proliferation and expansion of primary osteosarcoma cells. (2) MMPs cause overexpression of VEGF leading to new blood vessels formation. (3) Degradation of extracellular matrix and basic membranes by MMPs help malignant cells to invade in blood vessels. (4) Osteosarcoma cells arrested from endothelial cells of blood vessels in distant organs. (5) Tumor cells migrate in distant sites following blood circulation where they adhere. (6) Secondary tumors secrete MMPs in order to form a sufficient neoplastic blood vessels network. (7) Osteosarcoma cells in distant tissues create mature metastatic tumors [4]