Abstract 4869: Bone marrow-derived stromal cells contribute to a protumorigenic inflammatory environment that promotes drug resistance

Therapeutic resistance is a major cause of failure to eradicate cancer. Whereas mutational events are primarily responsible for the development of clones of tumor cells intrinsically resistant to therapy, the tumor microenvironment (TME) plays a critical role in allowing tumor cells to become transiently resistant to therapy before they acquire an irreversible form of resistance. The bone marrow, the site of metastasis of many cancers including neuroblastoma, represents a unique sanctuary for metastatic tumor cells that promotes this form of environment-mediated drug resistance (EMDR). Here we show that when exposed to neuroblastoma cell-derived exosomes, human bone marrow mesenchymal stromal cells (BMMSC) express multiple cytokines and chemokines that have a pro-tumorigenic function including interleukin (IL)-6, IL-8, vascular endothelial cell growth factor (VEGF)-A and macrophage chemotactic protein (MCP)-1 (CCL-2). Exposure of human neuroblastoma cells to conditioned medium (CM) of 48 hour co-cultures of tumor cells and BMMSC increased their resistance to the topoisomerase II inhibitor etoposide (ΔIC 50 = 0.73, p Citation Format: Lucia Borriello, Rie Nakata, Hong-Wei Wu, Robert C. Seeger, Yves A. DeClerck. Bone marrow-derived stromal cells contribute to a protumorigenic inflammatory environment that promotes drug resistance. [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 4869. doi:10.1158/1538-7445.AM2014-4869