Abstract 2847: Host angiopoietin-2 inhibits tumor growth and angiogenesis in the liver

Abstract

For growth and survival in metastasis, tumor colonies must develop new intratumoral vasculature for supply of nutrients and oxygen. Since angiopoietin-2 (Ang2) resulted in a burst of angiogenesis in the glioma model, we examined the effects of host Ang2 on colony growth and neo-angiogenesis during the liver colonization. Liver colonization was induced through the intrasplenic injection of MC38-GFP (murin colorectal carcinoma cells) into two genotype mice of the ang2−/− mice and the wild type mice. When colonies were established, the livers were isolated and analyzed using flow cytometry, immunoflorescent histochemistry and ELISA. In addition, the blood was collected from vena cava for measurement of MCP-1 at 14 days. Flow cytometry analyses of whole livers showed that the tumor cell population in the ang2−/− mice was approximately 2 times larger than in the wild type mice. Immunoflorescent histochemistry of the liver tissue using antibodies for CD31, CD34, CD146, VE-cadherin and NG2 showed that intratumoral vascular density and vascular maturity in the ang2−/− mice were approximately 2 times higher than the wild type mice. Intratumoral vessels were significantly positive for CD146 and CD34, markers more frequently associated with neo-angiogenesis, but much less for CD31. There was no significant difference in VEGF level which is known to mediate vascular response in combination with Ang2. CD11b positive cells and MCP-1 concentration in the livers were equivalent in two genotypes. Notably, there were approximately 10 times more Tie2+/CD11b+ cells in the ang2−/− mice than the wild type mice. CD11c+/CD45+ cell populations were slightly different in two genotypes. These results suggested that host Ang2 would inhibit tumor growth and neo-angiogenesis in the liver, and that the inhibition is correlated with the decreased recruitment of TEMs, one of myeloid cells, into the liver. 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 2847. doi:10.1158/1538-7445.AM2011-2847