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Hematopoietic Bone Marrow Progenitors Prepare Metastatic Sites

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NEW YORK (Reuters Health) Dec 07 - Before cancer cells spread to a metastatic site, certain hematopoietic bone marrow progenitors show up to prepare the area for invasion, according to a report in the December 8th issue of Nature. Moreover, blocking the function of these progenitors appears to prevent tumor metastasis.

Using murine models of cancer spread, Dr. David Lyden, from Cornell University in New York, and colleagues show that progenitors expressing vascular endothelial growth factor receptor 1 (VEGFR1) play a critical role in facilitating metastasis.

In the study, the VEGFR1-positive progenitors home in on pre-metastatic sites and form cell clusters. Blocking VEGFR1 function with antibodies or removing the progenitors from the bone marrow stopped these clusters from forming, which, in turn, prevented metastasis. Conversely, reconstituting knockout mice with VEGFR1-positive cells allowed metastasis to occur.

Further analysis showed that the progenitors express a protein called VLA-4 and that fibronectin, a fibroblast protein upregulated by tumor growth factors, is a ligand for VLA-4.

"These findings," the authors conclude, "demonstrate a requirement for VEGFR1-positive hematopoietic progenitors in the regulation of metastasis, and suggest that expression patterns of fibronectin and VEGFR1-positive, VLA-4-positive clusters dictate organ-specific tumor spread."

Nature 2005;438:820-827.