In vivo imaging reveals specialized bone marrow endothelial microdomains that support tumor engraftment. The study shows that murine bone marrow contains unique vascular regions defined by specialized endothelium expressing E-selectin and SDF-1, which localize the homing of various tumor cell lines. Disruption of SDF-1/CXCR4 interactions inhibits Nalm-6 cell homing to these vessels. Circulating leukemic cells engraft around these vessels, suggesting that this vascular structure provides a microenvironment for early metastatic tumor spread in the bone marrow. Hematopoietic stem/progenitor cells and lymphocytes also localize to these microdomains, indicating that this vasculature may function in benign states to demarcate entry portals for cells into the marrow space. Tumor cells use similar tissue-homing mechanisms as benign leukocytes to transit to specific organs. In vitro and in vivo data show that tumors depend on selectin-, integrin-, and chemokine-mediated vascular cell adhesion events to identify and bind to vascular beds at sites of tissue entry. These molecular mechanisms enable efficient spread of malignancies to target organs. Differential expression of these endothelial signals among tissues controls the destination of cellular traffic, but the contributions of the vascular molecular framework to the regulation of complex cellular microenvironments remain to be fully elucidated. The bone marrow is a frequent site for solid tumor spread and a common site for leukemic cell metastasis. These observations suggest that the bone marrow provides an avid environment for circulating tumor lodgement and growth. The bone marrow is also a common source of latent or "minimal residual disease" following treatment, raising the possibility that specific anti-apoptotic "niches" for metastatic growth may exist. Understanding the biologic architecture of this host microenvironment has significant implications for our approach to tumor treatment. In vivo confocal imaging was used to examine the dynamic interactions of intravenously-injected tumor cells with the bone marrow microenvironment. The study found that Nalm-6 pre-B acute lymphoblastic leukemia cells arrested in specific vascular domains. Other cell lines, including human and murine leukemias, multiple myeloma, and solid tumors, also homed to these vascular microdomains. The endothelium in these BM regions expressed a unique combination of vascular cell adhesion molecules and/or chemokines capable of attracting a broad variety of tumor metastases. The study identified SDF-1 as a candidate chemokine mediating Nalm-6 homing to these vascular regions. SDF-1 is known to play a role in BM engraftment for various malignant tumors. The study also found that SDF-1 was expressed in vascular "hot spots" corresponding to the regions that attracted leukemic cells. E-selectin expression corresponded to the pattern of SDF-1 positivity and was distinctly limited to vessels that supported leukemic cell engraftment. The study evaluated the functional roleIn vivo imaging reveals specialized bone marrow endothelial microdomains that support tumor engraftment. The study shows that murine bone marrow contains unique vascular regions defined by specialized endothelium expressing E-selectin and SDF-1, which localize the homing of various tumor cell lines. Disruption of SDF-1/CXCR4 interactions inhibits Nalm-6 cell homing to these vessels. Circulating leukemic cells engraft around these vessels, suggesting that this vascular structure provides a microenvironment for early metastatic tumor spread in the bone marrow. Hematopoietic stem/progenitor cells and lymphocytes also localize to these microdomains, indicating that this vasculature may function in benign states to demarcate entry portals for cells into the marrow space. Tumor cells use similar tissue-homing mechanisms as benign leukocytes to transit to specific organs. In vitro and in vivo data show that tumors depend on selectin-, integrin-, and chemokine-mediated vascular cell adhesion events to identify and bind to vascular beds at sites of tissue entry. These molecular mechanisms enable efficient spread of malignancies to target organs. Differential expression of these endothelial signals among tissues controls the destination of cellular traffic, but the contributions of the vascular molecular framework to the regulation of complex cellular microenvironments remain to be fully elucidated. The bone marrow is a frequent site for solid tumor spread and a common site for leukemic cell metastasis. These observations suggest that the bone marrow provides an avid environment for circulating tumor lodgement and growth. The bone marrow is also a common source of latent or "minimal residual disease" following treatment, raising the possibility that specific anti-apoptotic "niches" for metastatic growth may exist. Understanding the biologic architecture of this host microenvironment has significant implications for our approach to tumor treatment. In vivo confocal imaging was used to examine the dynamic interactions of intravenously-injected tumor cells with the bone marrow microenvironment. The study found that Nalm-6 pre-B acute lymphoblastic leukemia cells arrested in specific vascular domains. Other cell lines, including human and murine leukemias, multiple myeloma, and solid tumors, also homed to these vascular microdomains. The endothelium in these BM regions expressed a unique combination of vascular cell adhesion molecules and/or chemokines capable of attracting a broad variety of tumor metastases. The study identified SDF-1 as a candidate chemokine mediating Nalm-6 homing to these vascular regions. SDF-1 is known to play a role in BM engraftment for various malignant tumors. The study also found that SDF-1 was expressed in vascular "hot spots" corresponding to the regions that attracted leukemic cells. E-selectin expression corresponded to the pattern of SDF-1 positivity and was distinctly limited to vessels that supported leukemic cell engraftment. The study evaluated the functional role