Tumor exosomes not only initiate pre-metastatic niche formation but also determine organotypic metastasis, a hypothesis proposed by Stephen Paget more than 120 years ago.

Lyden also found that tumor-secreted microvesicles, known as exosomes, initiate pre-metastatic niche via induction of vascular leakiness, stromal cell education, and immunoregulation through key proteins (i.e., oncoproteins, integrins) and nucleic acids in exosomes. Work in the pre-metastatic niche has been translated to clinical care leading to advances in prediction, imaging, and targeting of early metastatic disease progression. Lyden and his team to develop the concept of the 'pre-metastatic niche'. Remarkably, these microenvironments are generated prior to tumor cell arrival at these sites, an observation that led Dr. Lyden and his colleagues made a pivotal discovery in the metastatic cascade revealing that tumor-secreted factors induce the formation of microenvironments in distant organs conducive to tumor cell survival and outgrowth. Using pediatric and adult cancer models, Dr.

Early work in the Lyden Lab resulted in several fundamental discoveries that involve the role of bone marrow-derived stem and progenitor cells in tumor vasculogenesis and in metastasis.

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