On the origin of (CD105+) circulating endothelial cells

Michiel H. Strijbos; Cornelis Verhoef; Jan W. Gratama; Stefan Sleijfer

doi:10.1160/TH08-11-0762

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(02): 347-351
DOI: 10.1160/TH08-11-0762

Endothelium and Vascular Development

Schattauer GmbH

On the origin of (CD105+) circulating endothelial cells

Authors

Michiel H. Strijbos

¹Department of Medical Oncology, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
Cornelis Verhoef

²Department of Surgical Oncology, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
Jan W. Gratama

¹Department of Medical Oncology, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
Stefan Sleijfer

¹Department of Medical Oncology, Erasmus MC – Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

Abstract

Summary

Cells designated by the CellSearch™ assay as circulating endothelial cells (CEC) (CD146⁺/CD105⁺/CD45⁻ nuclear cells) are thought to derive from damaged vasculature.As CD105 has been suggested to be expressed by endothelial cells from malignant vasculature particularly, it is currently unknown whether this assay is suitable to determine CECs in non-malignant diseases.Also,more insight is needed whether CECs as detected by this assay predominantly measures CECs or also endothelial progenitor cells (EPCs), which originate from the bone marrow and reflect angiogenesis rather than vascular damage. CEC counts were determined in nine patients treated with isolated limb perfusion with tumour necrosis factor (TNF) a and melphalan, and in 10 healthy donors. Given the severe vascular damage caused by venesection and cannulation of the main vessels, we expected a significant increase in CEC counts in case CEC were of vascular rather than of bone marrow origin.Additionally, this finding, as well as the presence of CD105⁺ CEC in the blood of healthy controls, would confirm that healthy endothelial cells express CD105. Numbers of CD146⁺/CD105⁺/CD45⁻ nuclear CEC increased significantly after venesection and cannulation. After administration of TNF, a large fraction of non-intact, possibly apoptotic CEC appeared. This study shows that the Cell-Search™ assay detects CECs originating from damaged vasculature. Furthermore, CD105 expression is found on CEC from damaged normal vasculature rendering further exploration of the value of CEC determined by this assay worthwhile not only in malignant diseases but also in non malignant disorders characterised by vascular damage.

Keywords

Angiogenesis and inhibitors - endothelial cells - vascular cell markers

Full Text

References

References
1 Miller KD. E2100: a phase III trial of paclitaxel versus paclitaxel/bevacizumab for metastatic breast cancer. Clin Breast Cancer 2003; 03: 421-422.
2 Motzer RJ, Hutson TE, Tomczak P. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115-124.
3 Sandler A, Gray R, Perry MC. et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542-2550.
4 Therasse P, Arbuck SG, Eisenhauer EA. et al. New guidelines to evaluate the response to treatment in solid tumors European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000; 92: 205-216.
5 Khan SS, Solomon MA, McCoy Jr JP. Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry. Cytometry B Clin Cytom 2005; 64: 1-8.
6 Rowand JL, Martin G, Doyle GV. et al. Endothelial cells in peripheral blood of healthy subjects and patients with metastatic carcinomas. Cytometry A 2007; 71: 105-113.
7 Strijbos MH, Gratama JW, Kraan J. et al. Circulating endothelial cells in oncology: pitfalls and promises. Br J Cancer 2008; 98: 1731-1735.
8 Smirnov DA, Foulk BW, Doyle GV. et al. Global gene expression profiling of circulating endothelial cells in patients with metastatic carcinomas. Cancer Res 2006; 66: 2918-2922.
9 Elshal MF, Khan SS, Raghavachari N. et al. A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile. BMC Immunol 2007; 08: 29.
10 Strijbos MH, Rao C, Schmitz PI. et al. Correlation between circulating endothelial cell counts and plasma thrombomodulin levels as markers for endothelial damage. Thromb Haemost 2008; 100: 642-647.
11 Ding YT, Kumar S, Yu DC. The role of endothelial progenitor cells in tumour vasculogenesis. Pathobiology 2008; 75: 265-273.
12 Beerepoot LV, Mehra N, Vermaat JS. et al. Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. Ann Oncol 2004; 15: 139-145.
13 Woywodt A, Blann AD, Kirsch T. et al. Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol. J Thromb Haemost 2006; 04: 671-677.
14 Fonsatti E, Altomonte M, Nicotra MR. et al. Endoglin (CD105): a powerful therapeutic target on tumor-associated angiogenetic blood vessels. Oncogene 2003; 22: 6557-6563.
15 Fonsatti E, Altomonte M, Arslan P. et al. Endoglin (CD105): a target for anti-angiogenetic cancer therapy. Curr Drug Targets 2003; 04: 291-296.
16 Ten Hagen TL, Eggermont AM. Solid tumor therapy: manipulation of the vasculature with TNF. Technol Cancer Res Treat 2003; 02: 195-203.
17 Ten Hagen TL, Seynhaeve AL, Eggermont AM. Tumor necrosis factor-mediated interactions between inflammatory response and tumor vascular bed. Immunol Rev 2008; 222: 299-315.
18 Verhoef C, de Wilt JH, Grunhagen DJ. et al. Isolated limb perfusion with melphalan and TNF-alpha in the treatment of extremity sarcoma. Curr Treat Options Oncol 2007; 08: 417-427.
19 Cheifetz S, Bellon T, Cales C. et al. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem 1992; 267: 19027-19030.
20 Zhu HJ, Burgess AW. Regulation of transforming growth factor-beta signaling. Mol Cell Biol Res Commun 2001; 04: 321-330.
21 Wang JM, Kumar S, Pye D. et al. A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues. Int J Cancer 1993; 54: 363-370.
22 Goh SG, Calonje E. Cutaneous vascular tumours: an update. Histopathology 2008; 52: 661-673.
23 Requena L, Sangueza OP. Cutaneous vascular proliferation Part II. Hyperplasias and benign neoplasms. J Am Acad Dermatol 1997; 37: 887-922.