[Frontiers in Bioscience S1, 304-318, June 1, 2009]

Circulating endothelial cells as biomarkers for angiogenesis in tumor progression

Ines Martin-Padura, Francesco Bertolini

Division of Hematology-Oncology, Department of Medicine, European Institute of Oncology, 20141 Milan, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. CECs, CEPsand endothelial microparticles
3.1. Antigenic definition of CECs and CEPs: isolation and quantification
4. Other bone marrow-derived cells in tumor angiogenesis
5. Antiangiogenic therapies
5.1. Soluble and molecular surrogate markers for angiogenesis
5.2. CECs as biomarkers in cancer
5.3. CEPs in tumor-associated vessel growth
5.4. Can CECs and CEPs be used to determine the Optimal Biological Dose (OBD) of an anti-angiogenic drug?
5.5. Can CEPS be used as vehicles for anticancer treatments?
6. Genetic instability in endothelial cells
7. Endothelial cells in the niche
8. Conclusions
9. Acknowledgments
10. References

1. ABSTRACT

An increased number of circulating endothelial cells (CECs) and endothelial progenitor cells (CEPs) has been reported in cancer patients. CEPs are derived from the bone marrow and will, during angiogenesis, differentiate into endothelial cells. CECs are mature endothelial cells (ECs) released from the vessel intima during physiological endothelial turnover or as a result of tumor treatment. Preclinical studies have shown that during tumor progression, the amount of circulating CECs correlates with angiogenesis. Moreover, there is growing evidence suggesting that CECs and CEPs viability and kinetics correlate with the patient responses to anti-angiogenic therapies. Thus, circulating CECs and CEPs may act as surrogate markers to test putative therapeutic efficacy. Moreover measuring CECs and CEPs may be useful to assess effects of antiangiogenic therapy.