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NIH Awards $2.2 Million to Fund Collaborative Research on the Role of Exosomes in Metastasis

Cancer metastasis - the spread of disease from the original site to a distant organ - remains a major challenge in treating cancer and a main cause of morbidity and mortality. A widely accepted explanation for this process - called "the seed and soil" hypothesis - recognizes the need for the cancer cell or "seed" to travel to a hospitable environment - the "soil.” To understand metastasis, many investigators have focused on the cancer cell- or seed. Yves DeClerck, MD, a pediatrician-scientist at Children's Hospital Los Angeles (CHLA) and co-leader of the Tumor Microenvironment Program at the USC-Norris Comprehensive Cancer Center, has studied this topic for his entire career from a slightly different perspective, concentrating on the "soil" or tumor microenvironment. Because of his recognition as a leader in this area, Dr. DeClerck was recently awarded $2.2 million from the National Cancer Institute, to investigate the microenvironment from a relatively new context. The study will focus on a newly identified type of messenger -- extracellular vesicles released by cancer cells into their environment. These vesicles, called exosomes, are small sacs shed by tumor cells that can contain protein, DNA, RNA and/or lipids. Exosomes are taken in by other cells and can modify the behavior of the receiving cell. According to Dr. DeClerck, healthy cells are typically inhospitable to cancer cells. What causes them to change from foe to friend? "There are different ways that cancer cells communicate with normal cells - causing the change - and one of these ways is through exosomes," said Dr. DeClerck, who is a Professor of Pediatrics and Biochemistry and Molecular Medicine at the Keck School of Medicine of USC. He also holds the Richard Call Family Endowed Chair in Pediatric Research Innovation at CHLA. Dr. DeClerck's collaborator on the NCI study is David Lyden, MD, of Weill Cornell Medical College, who originally proposed the role of tumor-secreted exosomes in cancer metastasis. The article in which Dr. Lyden made this proposal was published in the November 19, 2015 issue of Nature. This article is titled “Tumour exosome Integrins Determine Organotropic Metastasis.” Recently, Dr. DeClerck, along with collaborators at CHLA and Keck, published on this topic. The first paper, in the Journal of Extracellular Vesicles, describes research conducted during his sabbatical, spent in the laboratory of co-author Pascale Zimmermann in Marseille, France. His research identified how exosomes, shed by neuroblastoma cells, induce bone marrow mesenchymal progenitor cells to release factors favorable to cancer cells. This article, published online on June 25, 2017, is titled “Contribution of Neuroblastoma-Derived Exosomes to the Production of Pro-Tumorigenic Signals by Bone Marrow Mesenchymal Stromal Cells.” A subsequent paper, published online on September 1, 2017 in Cancer Research, describes the mechanisms by which these bone marrow cells - also present in primary tumors - promote the growth of neuroblastoma cells and their resistance to chemotherapy. This article is titled “Cancer-Associated Fibroblasts Share Characteristics and Protumorigenic Activity with Mesenchymal Stromal Cells.” "What if you could intervene early and prevent the cancer cell from modifying the bone marrow - keeping it inhospitable to cancer," said Dr. DeClerck. "Instead of figuring out how to treat metastatic disease, we could prevent it." This posting is based on a CHLA news release, dated September 5, 2017.

[Press release] [Nature abstract] [Journal of Extracellular Vesicles abstract] [Cancer Research abstract]