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Departments of 1 Pediatrics, 2 Cell and Developmental Biology, and 3 Genetic Medicine, Weill College of Medicine at Cornell University; and 4 Memorial Sloan-Kettering Cancer Center, New York, New York
Requests for reprints: David Lyden, Children's Cancer and Blood Foundation Laboratories, Box 284, 515 East 51st street, Weill Cornell Medical College, New York, NY 10021. Phone 212-746-3941; E-mail: dcl2001{at}med.cornell.edu.
Current focus on cancer metastasis has centered on the intrinsic factors regulating the cell autonomous homing of the tumor cells to the metastatic site. Specific up-regulation of fibronectin and clustering of bone marrow–derived cellular infiltrates coexpressing matrix metalloproteinases in distant tissue sites before tumor cell arrival are proving to be indispensable for the initial stages of metastasis. These bone marrow–derived hematopoietic progenitors that express vascular endothelial growth factor receptor 1 mobilize in response to the unique array of growth factors produced by the primary tumor. Their arrival in distant sites represents early changes in the local microenvironment, termed the "premetastatic niche," which dictate the pattern of metastatic spread. Focus on the early cellular and molecular events in cancer dissemination and selectivity will likely lead to new approaches to detect and prevent metastasis at its earliest inception. (Cancer Res 2006; 66(23): 11089-93)
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