Abstract
It has been shown that bone marrow–derived stem cells can form a major fraction of the tumor endothelium in mouse tumors. To determine the role of such cells in human tumor angiogenesis, we studied six individuals who developed cancers after bone marrow transplantation with donor cells derived from individuals of the opposite sex. By performing fluorescence in situ hybridization (FISH) with sex chromosome–specific probes in conjunction with fluorescent antibody staining, we found that such stem cells indeed contributed to tumor endothelium, but at low levels, averaging only 4.9% of the total. These results illustrate substantial differences between human tumors and many mouse models with respect to angiogenesis and have important implications for the translation of experimental antiangiogenic therapies to the clinic.
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Acknowledgements
We thank L. Brennan and C. Roberts (Dana-Farber Cancer Institute, Boston, Massachusetts) for help with obtaining clinical samples. We would also like to thank B. Schlegelberger (MH Hannover, Germany) and S. Popp (DKFZ Heidelberg, Germany) who provided helpful technical advice for combined IF-FISH, T.S. Bruce, and G. Parmigiani for his advice on statistical issues. This work was supported by National Institutes of Health grant CA57345.
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Supplementary information
Supplementary Fig. 1
Blood vessel from a female control sample of a submandibular mucoepidermoid carcinoma analyzed by FISH with a X-chromosome specific probe in conjunction with fluorescent antibody staining (PDF 34 kb)
Supplementary Table 1
Patients who developed cancers following bone marrow transplantation with donors of the opposite sex (PDF 11 kb)
Supplementary Table 2
Internal controls (PDF 11 kb)
Supplementary Table 3
Chimerism analysis of transplant patient samples (PDF 10 kb)
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Peters, B., Diaz, L., Polyak, K. et al. Contribution of bone marrow–derived endothelial cells to human tumor vasculature. Nat Med 11, 261–262 (2005). https://doi.org/10.1038/nm1200
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DOI: https://doi.org/10.1038/nm1200
