In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment.
Journal Article (Journal Article)
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 metastasis. 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.
Full Text
Duke Authors
Cited Authors
- Sipkins, DA; Wei, X; Wu, JW; Runnels, JM; Côté, D; Means, TK; Luster, AD; Scadden, DT; Lin, CP
Published Date
- June 16, 2005
Published In
Volume / Issue
- 435 / 7044
Start / End Page
- 969 - 973
PubMed ID
- 15959517
Pubmed Central ID
- PMC2570168
Electronic International Standard Serial Number (EISSN)
- 1476-4687
Digital Object Identifier (DOI)
- 10.1038/nature03703
Language
- eng
Conference Location
- England