Abstract 3593: Examining the role of tumor cell secreted factors in intravasation and enhancing paracrine loop invasion

Abstract

Abstract The interaction of breast cancer cells with other cells in the tumor microenvironment plays an important role in metastasis. Invasion and intravasation, two critical steps in the metastatic process, are thought to be influenced by these interactions in addition to their intrinsic invasive properties. Macrophages are of particular interest when it comes to studying tumor cell invasiveness. Previous studies have shown that there is paracrine loop signaling between breast cancer cells and macrophages in which colony stimulating factor 1 (CSF-1) produced by tumor cells stimulates epidermal growth factor (EGF) production by macrophages. This EGF, in turn, stimulates invasion of the tumor cells. In addition to the classically described paracrine loop, it has been seen that tumor cell expression of ErbB3, a member of the EGFR family of receptor tyrosine kinases, may play a role in facilitating tumor cell intravasation. Overexpression of ErbB3 in breast cancer patients correlates with decreased survival. We show that using a blocking antibody against ErbB3 results in a significant decrease in macrophage-induced transendothelial migration of breast cancer cells. Tumor cell secretion of Neuregulin 1 (NRG1), a ligand of the ErbB3 receptor, may also play a role in the tumor cell- macrophage paracrine interaction. We show that stimulation of macrophages with NRG1 upregulates mRNA expression of JAG1, a ligand of the Notch receptor. Activation of the Notch receptor pathway has been shown to be involved in the process of tumor cell invasion. Overall, our studies look to examine this interaction between tumor cells and macrophages and these observations indicate that ErbB3, NRG1, and JAG1 could serve as novel targets in metastasis and the tumor microenvironment. Citation Format: Ramon M. Cabrera, Zhen N. Zhou, Minna Roh-Johnson, John Condeelis, Dianne Cox, Jeffrey E. Segall. Examining the role of tumor cell secreted factors in intravasation and enhancing paracrine loop invasion. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3593. doi:10.1158/1538-7445.AM2014-3593