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Mechanisms of metastasis: Epithelial-to-mesenchymal transition and contribution of tumor microenvironment

Authors

  • Joyce C. Tse,

    1. Division of Matrix Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts
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  • Raghu Kalluri

    Corresponding author
    1. Division of Matrix Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
    2. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts
    3. Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts
    • Chief, Division of Matrix Biology, Beth Israel Deaconess Medical Center, 330, Brookline Avenue (DANA 514), Boston, MA 02215.
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    • Associate Professor of Medicine, Harvard Medical School.


Abstract

Every year about 500,000 people in the United States die as a result of cancer. Among them, 90% exhibit systemic disease with metastasis. Considering this high rate of incidence and mortality, it is critical to understand the mechanisms behind metastasis and identify new targets for therapy. In recent years, two broad mechanisms for metastasis have received significant attention: epithelial-to-mesenchymal transition (EMT) and tumor microenvironment interactions. EMT is believed to be a major mechanism by which cancer cells become migratory and invasive. Various cancer cells—both in vivo and in vitro—demonstrate features of epithelial-to-mesenchymal-like transition. In addition, many steps of metastasis are influenced by host contributions from the tumor microenvironment, which help determine the course and severity of metastasis. Here we evaluate the diverse mechanisms of EMT and tumor microenvironment interactions in the progression of cancer, and construct a rational argument for targeting these pathways to control metastasis. J. Cell. Biochem. 101: 816–829, 2007. © 2007 Wiley-Liss, Inc.

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