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Contribution of bone marrow–derived endothelial cells to human tumor vasculature

Nature Medicine volume 11, pages 261–262 (2005)Cite this article

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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Figure 1: Blood vessels of human tumors were analyzed by FISH with sex chromosome–specific probes (white) in conjunction with fluorescent antibody staining.

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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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Authors and Affiliations

  1. The Sidney Kimmel Comprehensive Cancer Center and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, 21231, Maryland, USA

    Brock A Peters, Luis A Diaz Jr, Leslie Meszler, Kathy Romans, Bert Vogelstein, Kenneth W Kinzler & Christoph Lengauer

  2. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 1650 Orleans Street, Baltimore, 21231, Maryland, USA

    Brock A Peters & Kenneth W Kinzler

  3. Department of Medical Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street D740C, Boston, 02115, Massachusetts, USA

    Kornelia Polyak & Joseph H Antin

  4. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street D740C, Boston, 02115, Massachusetts, USA

    Eva C Guinan

  5. Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, 110 Fairview Avenue N., G1-300, Seattle, 98109, Washington, USA

    David Myerson

  6. Departments of Pathology and Hematopathology, Division of Pathology and Laboratory Medicine, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 0085, Houston, 77030, Texas, USA

    Stanley R Hamilton

Authors
  1. Brock A Peters
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  2. Luis A Diaz Jr
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  3. Kornelia Polyak
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  4. Leslie Meszler
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  5. Kathy Romans
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  6. Eva C Guinan
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  7. Joseph H Antin
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  8. David Myerson
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  9. Stanley R Hamilton
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  10. Bert Vogelstein
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  11. Kenneth W Kinzler
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  12. Christoph Lengauer
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Corresponding author

Correspondence to Christoph Lengauer.

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The authors declare no competing financial interests.

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)

Supplementary Methods (PDF 12 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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