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Published in: Breast Cancer Research and Treatment 3/2007

01-12-2007 | Preclinical Study

Endothelial progenitor cells in breast cancer patients

Authors: Christiane Richter-Ehrenstein, Jörn Rentzsch, Sanyukta Runkel, Achim Schneider, Gilbert Schönfelder

Published in: Breast Cancer Research and Treatment | Issue 3/2007

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Abstract

Purpose

Development of new capillary blood vessels is essential for the growth of cancer. Two distinct processes, vasculogenesis and angiogenesis implement the formation of the new vascular network. Recently, it was demonstrated that vasculogenesis creates the primary network of vascular endothelial cells that will become major blood vessels in malignant tumors by the recruitment of CD34+/vascular endothelial growth factor receptor 2 (FLK-1)+ endothelial progenitor cells (EPCs) to sites of the new vessel formation with subsequent differentiation into mature endothelial cell. Therefore the aim of this study was a) to quantitate EPCs in breast cancer patients and b) to evaluate if the release of EPCs into the circulation is mainly regulated by the tumor himself.

Experimental design

CD34+FLK-1+ EPCs were measured in the peripheral circulation of patients with breast cancer (n = 47) before and after therapy. Furthermore the potential of EPCs to differentiate into endothelial cells was investigated by late-outgrowth experiments and the metabolic uptake of dil-acetylated-LDL and immunoreactivity against von Willebrand factor.

Results

In breast cancer patients the amount of CD34+FLK-1+ EPCs (percent of peripheral blood mononuclear cells) is significantly increased in women with breast cancer. Tumors larger than 2 cm showed significantly higher values of CD34+FLK-1+ EPCs. After excision of the tumor the amount of CD34+FLK-1+ EPCs rapidly declines.

Conclusions

Our findings lead to the tumor, as source of angiogenic chemokines, is most important for recruiting CD34+FLK-1+ EPCs during breast cancer development. Therefore circulating endothelial progenitor cells may work as a new diagnostic tool in the screening and diagnosis of breast cancer.
Literature
1.
go back to reference Goldmann E (1907) The growth of malignant disease in man and the lower animals with special reference to the vascular system. Lancet 2:1236–1240CrossRef Goldmann E (1907) The growth of malignant disease in man and the lower animals with special reference to the vascular system. Lancet 2:1236–1240CrossRef
2.
go back to reference Ide A, Baker NH, Warren SL (1939) Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Radiol 42:891–899 Ide A, Baker NH, Warren SL (1939) Vascularization of the Brown-Pearce rabbit epithelioma transplant as seen in the transparent ear chamber. Am J Radiol 42:891–899
3.
go back to reference Algire GH, Chalkley HW (1945) Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst USA 6:73–85 Algire GH, Chalkley HW (1945) Vascular reactions of normal and malignant tissues in vivo. I. Vascular reactions of mice to wounds and to normal and neoplastic transplants. J Natl Cancer Inst USA 6:73–85
4.
go back to reference Folkman J (2000) In: Holland JF et al (eds) Cancer medicine. Decker, Ontario, Canada, pp 132–152 Folkman J (2000) In: Holland JF et al (eds) Cancer medicine. Decker, Ontario, Canada, pp 132–152
5.
go back to reference Asahara T, Masuda H, Takahashi T et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularisation. Circ Res 85:221–228PubMed Asahara T, Masuda H, Takahashi T et al (1999) Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularisation. Circ Res 85:221–228PubMed
6.
go back to reference Gehling UM, Ergün S, Schumacher U et al (2000) In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 95:3106–3112PubMed Gehling UM, Ergün S, Schumacher U et al (2000) In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood 95:3106–3112PubMed
7.
go back to reference Lyden D, Hattori K, Dias S et al (2001) Impaired recruitment of bone-marrow-derived endothelial and haematopoetic precursor cells blocks tumor angiogenesis and growth. Nature Med 7:1194–1201PubMedCrossRef Lyden D, Hattori K, Dias S et al (2001) Impaired recruitment of bone-marrow-derived endothelial and haematopoetic precursor cells blocks tumor angiogenesis and growth. Nature Med 7:1194–1201PubMedCrossRef
8.
go back to reference Reyes M, Dudek A, Jahagirgar B et al (2002) Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109:337–346PubMedCrossRef Reyes M, Dudek A, Jahagirgar B et al (2002) Origin of endothelial progenitors in human postnatal bone marrow. J Clin Invest 109:337–346PubMedCrossRef
9.
go back to reference Asahara T, Takahashi T, Masuda H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972PubMedCrossRef Asahara T, Takahashi T, Masuda H et al (1999) VEGF contributes to postnatal neovascularization by mobilizing bone marrow-derived endothelial progenitor cells. EMBO J 18:3964–3972PubMedCrossRef
10.
go back to reference Shi Q, Rafii S, Wu MHD et al (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367PubMed Shi Q, Rafii S, Wu MHD et al (1998) Evidence for circulating bone marrow-derived endothelial cells. Blood 92:362–367PubMed
11.
go back to reference Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967PubMedCrossRef Asahara T, Murohara T, Sullivan A et al (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967PubMedCrossRef
12.
go back to reference Lin Y, Weisdorf D, Solovey A, et al (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105:71–77PubMedCrossRef Lin Y, Weisdorf D, Solovey A, et al (2000) Origins of circulating endothelial cells and endothelial outgrowth from blood. J Clin Invest 105:71–77PubMedCrossRef
13.
go back to reference Gill M, Dias S, Hattori K et al (2001) Vascular Trauma Induces Rapid but Transient Mobilization of VEGFR2+ AC133+ Endothelial Precursor Cells. Circ Res 88:167–174PubMed Gill M, Dias S, Hattori K et al (2001) Vascular Trauma Induces Rapid but Transient Mobilization of VEGFR2+ AC133+ Endothelial Precursor Cells. Circ Res 88:167–174PubMed
14.
go back to reference Peichev M, Naiyer A, Pereira D et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors. Blood 95:952–958PubMed Peichev M, Naiyer A, Pereira D et al (2000) Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors. Blood 95:952–958PubMed
15.
go back to reference Quirici N, Soligo D, Caneva L et al (2001) Differentiation and expansion of endothelial cells from human bone marrow CD133+ cells. Br J Haematol 115:186–194PubMedCrossRef Quirici N, Soligo D, Caneva L et al (2001) Differentiation and expansion of endothelial cells from human bone marrow CD133+ cells. Br J Haematol 115:186–194PubMedCrossRef
16.
go back to reference Hristov M, Erl W, Weber P (2003) Endothelial progenitor cells. Mobilization differentiation, and homing. Arterioscler Thromb Vasc Biol 23:1–6CrossRef Hristov M, Erl W, Weber P (2003) Endothelial progenitor cells. Mobilization differentiation, and homing. Arterioscler Thromb Vasc Biol 23:1–6CrossRef
17.
go back to reference Rafii S (2000) Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest 105:17–19PubMed Rafii S (2000) Circulating endothelial precursors: mystery, reality, and promise. J Clin Invest 105:17–19PubMed
18.
go back to reference Lyden D, Young A, Zagzag D et al (1999) Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401:670–677PubMedCrossRef Lyden D, Young A, Zagzag D et al (1999) Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401:670–677PubMedCrossRef
19.
go back to reference Carmeliet P, Moons L, Luttun A et al (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7:575–583PubMedCrossRef Carmeliet P, Moons L, Luttun A et al (2001) Synergism between vascular endothelial growth factor and placental growth factor contributes to angiogenesis and plasma extravasation in pathological conditions. Nat Med 7:575–583PubMedCrossRef
20.
go back to reference Rafii S, Lyden D, Benezra R et al (2002) Vascular and haematopoietic stem cells: Novel targets for anti-angiogenesis therapy? Nature Cancer Rev 2:826–835CrossRef Rafii S, Lyden D, Benezra R et al (2002) Vascular and haematopoietic stem cells: Novel targets for anti-angiogenesis therapy? Nature Cancer Rev 2:826–835CrossRef
21.
go back to reference Bergers G, Brekken R, McMahon G et al (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature Cell Biololy 2:737–744CrossRef Bergers G, Brekken R, McMahon G et al (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nature Cell Biololy 2:737–744CrossRef
22.
go back to reference Heissig B, Hattori K, Dias S et al (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9mediated release of Kit-ligand. Cell 109:625–637PubMedCrossRef Heissig B, Hattori K, Dias S et al (2002) Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9mediated release of Kit-ligand. Cell 109:625–637PubMedCrossRef
23.
go back to reference Bertolini F, Paul S, Mancuso P et al (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63:4342–4346PubMed Bertolini F, Paul S, Mancuso P et al (2003) Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. Cancer Res 63:4342–4346PubMed
24.
go back to reference Kraft A, Weindel K, Ochs A et al (1999) Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer 85:178–187PubMedCrossRef Kraft A, Weindel K, Ochs A et al (1999) Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer 85:178–187PubMedCrossRef
25.
go back to reference Yamamoto Y, Toi M, Kondo S et al (1996) Concentrations of vascular endothelial growth factor in sera of normal controls and cancer patients. Clin Cancer Res 2:821–826PubMed Yamamoto Y, Toi M, Kondo S et al (1996) Concentrations of vascular endothelial growth factor in sera of normal controls and cancer patients. Clin Cancer Res 2:821–826PubMed
Metadata
Title
Endothelial progenitor cells in breast cancer patients
Authors
Christiane Richter-Ehrenstein
Jörn Rentzsch
Sanyukta Runkel
Achim Schneider
Gilbert Schönfelder
Publication date
01-12-2007
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2007
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9505-z

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