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Letter

Nature 435, 969-973 (16 June 2005) | doi:10.1038/nature03703; Received 23 February 2005; Accepted 3 May 2005

In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment

Dorothy A. Sipkins1,2,3, Xunbin Wei1, Juwell W. Wu1, Judith M. Runnels1, Daniel Côté1, Terry K. Means4, Andrew D. Luster4, David T. Scadden2,3,5 & Charles P. Lin1

  1. Wellman Center for Photomedicine, and
  2. Center for Regenerative Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, Massachusetts 02114, USA
  3. Department of Hematology-Oncology, Massachusetts General Hospital and Dana-Farber Cancer Institute, Harvard Medical School, and
  4. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital East, Harvard Medical School, Building 149, 13th Street, Charlestown, Massachusetts 02129, USA
  5. Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA

Correspondence to: Dorothy A. Sipkins1,2,3Charles P. Lin1 Correspondence and requests for materials should be addressed to C.P.L. (Email: lin@helix.mgh.harvard.edu) or D.A.S. (Email: dsipkins1@partners.org).

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The organization of cellular niches is known to have a key role in regulating normal stem cell differentiation and regeneration, but relatively little is known about the architecture of microenvironments that support malignant metastasis1, 2. Using dynamic in vivo confocal imaging, here we show that murine bone marrow contains unique anatomic regions defined by specialized endothelium. This vasculature expresses the adhesion molecule E-selectin and the chemoattractant stromal-cell-derived factor 1 (SDF-1) in discrete, discontinuous areas that influence the homing of a variety of tumour cell lines. Disruption of the interactions between SDF-1 and its receptor CXCR4 inhibits the homing of Nalm-6 cells (an acute lymphoblastic leukaemia cell line) to these vessels. Further studies revealed that circulating leukaemic cells can engraft around these vessels, suggesting that this molecularly distinct vasculature demarcates a microenvironment for early metastatic tumour spread in bone marrow. Finally, purified haematopoietic stem/progenitor cells and lymphocytes also localize to the same microdomains, indicating that this vasculature might also function in benign states to demarcate specific portals for the entry of cells into the marrow space. Specialized vascular structures therefore appear to delineate a microenvironment with unique physiology that can be exploited by circulating malignant cells.