Dr. David Lyden has made several fundamental discoveries which involve the role of bone marrow-derived stem and progenitor cells in tumor vasculogenesis and in metastasis. His laboratory showed the first evidence of genetic regulation in vasculogenesis with the discovery of one family of genes called Id1-4 in early blood vessel development in embryogenesis and in tumorigenesis (Nature 1999, 401:670-677). He and his colleagues were the first to identify two bone marrow-derived cells, endothelial progenitor cells (EPCs) and hematopoietic progenitor cells (HPCs) that both participate in the formation of new blood vessels in the primary tumor that occurred by vasculogenesis as opposed to angiogenesis or branching from pre-established blood vessels (Nature Medicine 2001, 9:702-712). This work has initiated other investigations of various populations of bone marrow-derived cells in tumor biology.
In recent years, his team has shown evidence that growth factors secreted by the primary tumor prime certain tissues for tumor cell engraftment (Nature 2005, 438:820-827). In response to these soluble factors, tumor associated cells such as hematopoietic progenitor cells cluster at ‘pre-metastatic niches’ creating an environment that is conducive for tumor cell adhesion and invasion. At the pre-metastatic niche, newly recruited myeloid cells collaborate with other cells types residing in the tissue parenchyma. Together, these cells provide a platform of chemokines, growth factors, matrix-degrading enzymes and adhesion molecules, thereby accelerating assembly of the metastatic lesion. This model suggests that it may be beneficial for systemic therapies targeted to the metastatic microenvironment to be used early, perhaps even as an adjunct to the initial treatment of the primary tumor (Nature Reviews Cancer, 2009 9:285-293). Finally, there is the implication that treatments may need to be tailored to each stage of metastatic progression: pre-metastatic, micrometastatic and macrometastatic.