Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Antigen expression profile in circulating endothelial progenitor cells

Nature Reviews Cancer volume 7, page 68 (2007)Cite this article

A Correspondence to this article was published on 01 January 2007

Access through your institution
Buy or subscribe

The clinical applications of discoveries in angiogenesis and vasculogenesis research necessitate the development and validation of surrogate markers of tumour neovascularization and anti-angiogenic drug efficacy. Candidate biomarkers include circulating endothelial cells (CECs) shed by the tumour vasculature and circulating endothelial progenitors (CEPs) derived from the bone marrow, both measured by multiparametric flow cytometry. In their remarkable Review1, Bertolini and colleagues define CEPs as expressing low levels of the pan-haematopoietic antigen CD45 (CD45dim) (Figure 1). However, in the same article their flow cytometry approach consists of excluding all haematopoietic cells by sequential gating, thereby only selecting CD45-negative cells for further analyses (page 837 and Figure 2). Although the exact identity and function of CEPs is the subject of debate, these seemingly contradictory statements merit clarification. CEPs, defined as CD34+CD133+CD45dim, CD34+VEGFR2+CD45dim or CD34+CD133+VEGFR2+CD45dim cells, have been reported to be present in the peripheral blood of cancer patients2,3, cardiac patients4 and smokers5 as well as in umbilical cord blood2. Nevertheless, the lack of haematopoietic antigen expression, such as CD45, has also been used to show the endothelial nature of CEPs and CECs6,7. In addition, studies in murine models have documented the existence of bone-marrow-derived SCA1+FLK1+CD45+ and SCA1+TIE2+CD31+CD45+ endothelial precursor cell populations8,9. These differences might reflect, in part, our limited understanding of the potential origin and steps of differentiation of CEPs toward the endothelial lineage in postnatal vasculogenesis10,11. In light of the growing interest in vasculogenesis and anti-angiogenic therapy trials, we encourage the authors to clarify the issue.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Bertolini, F., Shaked, Y., Mancuso, P. & Kerbel, R. S. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nature Rev. Cancer 6, 835–845 (2006).

    Article  CAS  Google Scholar 

  2. Duda, D. G. et al. Differential CD146 expression on circulating versus tissue endothelial cells in rectal cancer patients: implications for circulating endothelial and progenitor cells as biomarkers for antiangiogenic therapy. J. Clin. Oncol. 24, 1449–1453 (2006).

    Article  CAS  Google Scholar 

  3. Fürstenberger, G. et al. Circulating endothelial cells and angiogenic serum factors during neoadjuvant chemotherapy of primary breast cancer. Br. J. Cancer 94, 524–531 (2006).

    Article  Google Scholar 

  4. Numaguchi, Y. et al. The impact of the capability of circulating progenitor cell to differentiate on myocardial salvage in patients with primary acute myocardial infarction. Circulation 114 (suppl. I), I114–I119 (2006).

    PubMed  Google Scholar 

  5. Kondo, T. et al. Smoking cessation rapidly increases circulating progenitor cells in peripheral blood in chronic smokers. Arterioscler. Thromb. Vasc. Biol. 24, 1442–1447 (2004).

    Article  CAS  Google Scholar 

  6. Blann, A. D. et al. Circulating endothelial cells. Biomarker of vascular disease. Thromb. Haemost. 93, 228–235 (2005).

    Article  CAS  Google Scholar 

  7. Ingram, D. A., Caplice, N. M. & Yoder, M. C. Unresolved questions, changing definitions, and novel paradigms for defining endothelial progenitor cells. Blood 106, 1525–1531 (2005).

    Article  CAS  Google Scholar 

  8. Shaw, J. P., Basch, R. & Shamamian, P. Hematopoietic stem cells and endothelial cell precursors express Tie-2, CD31 and CD45. Blood Cells Molec. Dis. 32, 168–175 (2004).

    Article  CAS  Google Scholar 

  9. Qin, G. et al. Functional disruption of α4 integrin mobilizes bone-marrow-derived endothelial progenitors and augments ischemic neovascularization. J. Exp. Med. 203, 153–163 (2006).

    Article  CAS  Google Scholar 

  10. Urbich, C. & Dimmeler, S. Endothelial progenitor cells. Characterization and role in vascular biology. Circ. Res. 95, 343–353 (2004).

    Article  CAS  Google Scholar 

  11. Porat, Y. et al. Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages. Br. J. Haematol. 135, 703–714 (2006).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, S.A. Localio Laboratory for Surgical Research, New York University School of Medicine, New York, 10016, NY, USA

    Jean-Pierre Gagner & Peter Shamamian

  2. New York University Cancer Institute, New York University School of Medicine, New York, 10016, NY, USA

    Peter Shamamian

Authors
  1. Jean-Pierre Gagner
    View author publications

    Search author on:PubMed Google Scholar

  2. Peter Shamamian
    View author publications

    Search author on:PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gagner, JP., Shamamian, P. Antigen expression profile in circulating endothelial progenitor cells. Nat Rev Cancer 7, 68 (2007). https://doi.org/10.1038/nrc1971-c1

Download citation

  • Issue date:

  • DOI: https://doi.org/10.1038/nrc1971-c1

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing