Abstract 5288: Tumor-endothelial 3D spheroids for dynamic imaging of cancer progression

Abstract

Abstract The increasing use of anti-angiogenic drugs for the treatment of cancer has emerged from the explosion of knowledge about the process of tumor angiogenesis. However, the clinical results of using such drugs have been relatively modest and new agents are likely needed. A robust pre-clinical model of cellular mechanisms governing tumor angiogenesis may improve our ability to develop strategies for tumor specific drug delivery with superior pharmacokinetics, controlled biodistribution, efficacy, and safety profiles. We have developed a system to grow 3D-cultures of tumor and endothelial cells in hanging drops of medium. Subsequently, we transplant these spheroidal cultures into the dorsal skin fold window chamber of mice for intravital multiphoton imaging of neovasculature and disease progression. Our initial observation was that there was a marked difference in neovascularization from the GFP-tumor-endothelial spheroids in comparison to GFP-tumor spheroids in the window chamber mouse model. Molecular analysis using an antibody array showed a pronounced upregulation of angiogenic factors in the tumor tissue derived from the tumor-endothelial spheroid compared to the spheroid grown with tumor cells alone. Interleukin-1α, FGF-1α, CCN3/NOV, PIGF-2, MMP-3, MMP-8 and MMP-9 were seven identified proteins that showed distinct differences in expression between the two spheroid types. Further, the relative increase in tumor growth of tumor-endothelial spheroids implanted on the rear hind limb was much faster than the tumor cell alone spheroid and resulted in evidence of greater metastasis to the lung. We thus strongly believe that the 3D tumor-endothelial spheroid implanted in the dorsal fold window chamber of mice is a more realistic and informative model for dynamic imaging of critical aspects of tumor angiogenesis and the study of metastasis. Efforts are underway to monitor molecular and cellular events related to radiation exposure combined with anti-angiogenic agents of varying mechanisms of action to determine prudent new avenues for therapeutic success. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5288. doi:10.1158/1538-7445.AM2011-5288