Three-Dimensional (3D) Imaging of Tumor Angiogenesis and its Inhibition: Evaluation of Tumor Vascular-Targeting Agent Efficacy in the DMBA-induced Rat Breast Cancer Model by Confocal Laser Scanning Microscopy (CLSM)

Abstract

There is considerable interest in tumor angiogenesis and its inhibition, because tumor angiogenesis plays an important role in tumor growth and distant metastasis, and is highly associated with overall survival and relapse free-survival in cancer patients. This study was performed to determine the mechanisms underlying tumor angiogenesis and its inhibition using the angiogenesis inhibitor TNP 470 and antimitotic drug, docetaxel (Taxotere). Variable 3D image analysis of tumor vasculature after chemotherapy was performed by CLSM using the DMBA-induced rat breast cancer model. 3D images of the vasculature in DMBA-induced rat breast cancer were characterized by increased microvessel density and anastomosing, irregularly branched microvessel networks. After administration of TNP-470 or docetaxel, tumor microvessel density was markedly decreased and tumor microvessel networks were markedly destroyed. Furthermore, tumor microvessels less than 30 μm in diameter were not found. The remaining tumor microvessels (30-60 μm in diameter) were mainly localized in the periphery of the tumor. These observations suggest that docetaxel might have the ability to inhibit tumor angiogenesis as well as TNP-470. CLSM with the FI method is a valuable technique for estimation of the efficacy of anti-angiogenic chemotherapy.