THREE-DIMENSIONAL MODEL OF METASTATIC TUMOR ANGIOGENESIS IN RESPONSE TO ANTI-ANGIOGENIC FACTOR ANGIOSTATIN

Surgeons observed that primary tumors are capable of suppressing the growth of their metastases by generating anti-angiogenic factor angiostatin. A three-dimensional (3D) mathematical model of development of the metastatic tumor vasculature is presented to simulate the morphology and construction of 3D microvascular networks under the inhibitory effect of antiangiogenic factor angiostatin excreted by the primary tumor. The simulation results demonstrate that metastatic tumor microvascular density (MVD) decreases by about 60%, 58% and 52%, respectively, at t = 3, 7 and 14 days under the effect of anti-angiogenic factor angiostatin. The abnormal geometric and morphological features of 3D microvasculature networks inside and outside the metastatic tumor improve in the presence of angiostatin. The present model may allow to simulate experimental tests and may provide theoretical models for clinical research of anti-angiogenic therapy strategies.