Investigating the mechanisms of metastasis
Children's Hospital Los Angeles news Sep 09, 2017
Cancer metastasis remains a major challenge in treating cancer and a main cause of morbidity and mortality. A widely accepted explanation for this process  called Âthe seed and soil hypothesis  recognizes the need for the cancer cell or Âseed to travel to a hospitable environment  the ÂsoilÂ.
To understand metastasis, many investigators have focused on the cancer cell  or seed. Yves DeClerck, MD, a pediatrician-scientist at ChildrenÂs Hospital Los Angeles 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 Âsoil or tumor microenvironment. Because of his recognition as a leader in this area, 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 contain protein, DNA, RNA and lipids. Exosomes are taken in by other cells and can modify behavior of the receiving cell.
According to DeClerck, healthy cells are typically inhospitable to cancer cells. What causes them to change from foe to friend? ÂThere are different ways that cancer cells communicate with normal cells  causing the change  and one of these ways is through exosomes, said 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.
DeClerckÂs 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.
Recently 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 lab 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. A subsequent paper, recently published in the journal 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.
ÂWhat if you could intervene early and prevent the cancer cell from modifying the bone marrow  keeping it inhospitable to cancer, said DeClerck. ÂInstead of figuring out how to treat metastatic disease, we could prevent it.Â
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To understand metastasis, many investigators have focused on the cancer cell  or seed. Yves DeClerck, MD, a pediatrician-scientist at ChildrenÂs Hospital Los Angeles 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 Âsoil or tumor microenvironment. Because of his recognition as a leader in this area, 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 contain protein, DNA, RNA and lipids. Exosomes are taken in by other cells and can modify behavior of the receiving cell.
According to DeClerck, healthy cells are typically inhospitable to cancer cells. What causes them to change from foe to friend? ÂThere are different ways that cancer cells communicate with normal cells  causing the change  and one of these ways is through exosomes, said 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.
DeClerckÂs 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.
Recently 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 lab 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. A subsequent paper, recently published in the journal 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.
ÂWhat if you could intervene early and prevent the cancer cell from modifying the bone marrow  keeping it inhospitable to cancer, said DeClerck. ÂInstead of figuring out how to treat metastatic disease, we could prevent it.Â
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