Abstract 403: Interaction of carbon nanotubes with macrophages in tumor microenvironment
Authors: Jie Meng, Man Yang, Jing Lei, Jian Liu, Xuelian Cheng, Hua Kong, Haiyan Xu
Journal: Cancer Research (2012)

Abstract Macrophages take on different phenotypes and play different roles in tumor progress as well as anti-tumor therapy depending on the environmental signals that they receive. We have previously reported that subcutaneously injected oxidized multiwalled carbon nanotubes (o-MWCNTs) in normal BABL/c mice were largely engulfed by resident macrophages around the injection site, inducing complement activation and short-term upregulation of inflammatory cytokines [Jie Meng, Man Yang, Zhen Xu, Fumin Jia, Hua Kong, and Haiyan Xu. Immune responses of BALB/c mice to subcutaneously injected multi-walled carbon nanotubes. Nanotoxicology, 2010, DOI:10.3109/17435390.2010.523483]; subcutaneous injection of o-MWCNTs in tumor bearing BALB/c mice upregulated the expression of GM-CSF and IL12p70 in the serum over 2-fold increase and inhibited the tumor progression to a certain extent [Jie Meng, Man Yang, Fumin Jia, Hua Kong, Weiqi Zhang, ChaoyingWang, Jianmin Xing, Sishen Xie and Haiyan Xu. Subcutaneous injection of water-soluble multi-walled carbon nanotubes in tumor-bearing mice boosts the host immune activity. Nanotechnology 2010; 21: 145104]. When o-MWCNTs were used as a carrier of tumor lysate, subcutaneous injection of this conjugate in tumor-bearing mice effectively increased cytotoxicity of the lymphocytes to the tumor cells [Jie Meng, Jie Meng, Jinhong Duan, Hua Kong, Chen Wang, Sishen Xie, Shuchang Chen, Haiyan Xu and Xian-Da Yang. Carbon Nanotubes Conjugated to Tumor Lysate Protein Enhance the Efficacy of an Anti-tumor Immunotherapy. Small 2008; 4(9): 1364-1370]. These findings imply that the inhibitory effect of o-MWCNTs on tumor progression may be associated with their interactions with macrophages. The present work focused on the effect of o-MWCNTs on macrophages phenotypes and functions in the tumor environment. The o-MWCNTs were physicochemically characterized with SEM, DLS, FTIR, TGA, and UV-vis-NIR spectroscopy; and the effects on RWA 264.7 cell line or macrophages in breast cancer tumor-bearing mice were investigated using MTS assay, flow cytometry analysis, and histological and immunohistochemical observations. Experimental results showed that subcutaneously injected o-MWCNTs not only attracted resident macrophages in tissue and induced phagocytosis, but also competitively recruited macrophages from circulating monocytes, which led to reduction of macrophages and vessel density around the tumor mass and inhibition of tumor progression and metastasis in the lung. Additionally, o-MWCNTs inhibited the ability of alternatively activated RAW macrophages to promote tumor cells migration as well as decreased their proliferation rate. Acknowledgement: This work was supported by National Key Scientific Projects of China (2011CB933504, 2010CB934002) and Beijing Municipal Natural Science Foundation (2011022). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 403. doi:1538-7445.AM2012-403