Abstract

Tumor-derived Exosomes Contribute to a Pro-inflammatory Tumor Microenvironment through the Stimulation of Chemokines and Cytokines in Mesenchymal Stromal Cells and Macrophages

Yves A. DeClerck, Professor of Pediatrics and Biochemistry & Molecular Medicine, Children’s Hospital Los Angeles, University of Southern California

Exosomes are members of a large family of extracellular vesicles involved in cell-cell communication that play important regulatory functions in physiological and pathological conditions. Using neuroblastoma (NB), the second most common solid tumor in children and a cancer that is highly metastatic to the bone marrow and the liver as a model, we show that NB-derived exosomes contribute to the stimulation of several protumorigenic cytokines and chemokines (IL-6, IL-8, MCP-1, VEGF) by mesenchymal stromal cells (MSC) and macrophages via ERK1/2 activation.  In vivo NB-derived exosomes are also preferentially captured by macrophages at the site of metastasis (bone marrow and liver).  Altogether these cytokines promotes the proliferation of tumor cells, their resistance to chemotherapy and immune escape via STAT3 and ERK1/2 activation.