Circulating endothelial cells, endothelial progenitor cells, and endothelial microparticles in cancer.

Cancer, a proliferative disease hallmarked by abnormal cell growth and spread, is largely dependent on tumor neoangiogenesis, with evidence of vascular endothelial dysfunction. Novel ways to assess vascular function in cancer include measuring levels of circulating endothelial cells (CEC). Rare in healthy individuals, increased CEC in peripheral blood reflects significant vascular damage and dysfunction. They have been documented in many human diseases, including different types of cancers. An additional circulating cell population are endothelial progenitor cells (EPC), which have the ability to form endothelial colonies in vitro and may contribute toward vasculogenesis. At present, there is great interest in evaluating the role of EPC as novel markers for tumor angiogenesis and drug therapy monitoring. Recently, exocytic procoagulant endothelial microparticles (EMP) have also been identified. CEC, EPC, and EMP research works may have important clinical implications but are often impeded by methodological issues and a lack of consensus on phenotypic identification of these cells and particles. This review aims to collate existing literature and provide an overview on the current position of CEC, EPC, and EMP in cell biology terms and to identify their significance to clinical medicine, with particular emphasis on relationship with cancer.

[1]  F Dignat-George,et al.  Detection of circulating endothelial cells and endothelial progenitor cells by flow cytometry , 2006, Cytometry. Part B, Clinical cytometry.

[2]  B. Garmy-Susini,et al.  Circulating endothelial progenitor cells , 2005, British Journal of Cancer.

[3]  Hong Zhang,et al.  Circulating endothelial progenitor cells in multiple myeloma: implications and significance. , 2005, Blood.

[4]  G. Watkins,et al.  Assessing microvessels and angiogenesis in human breast cancer, using VE‐cadherin , 2005, Histopathology.

[5]  M. Corada,et al.  VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly. , 2005, Blood.

[6]  S. Shirasawa,et al.  Oncogenic events regulate tissue factor expression in colorectal cancer cells: implications for tumor progression and angiogenesis. , 2005, Blood.

[7]  G. Lip,et al.  Circulating endothelial cells, von Willebrand factor, interleukin-6, and prognosis in patients with acute coronary syndromes. , 2005, Blood.

[8]  P. Micco Inside the two way association between malignancy and alteration of haemostasis. , 2004 .

[9]  E. D. de Vries,et al.  Endothelial cell effects of cytotoxics: balance between desired and unwanted effects. , 2004, Cancer treatment reviews.

[10]  E. Voest,et al.  Circulating endothelial cells in cancer patients do not express tissue factor. , 2004, Cancer letters.

[11]  Gregory Y H Lip,et al.  Endothelial Dysfunction and Damage in Congestive Heart Failure: Relation of Flow-Mediated Dilation to Circulating Endothelial Cells, Plasma Indexes of Endothelial Damage, and Brain Natriuretic Peptide , 2004, Circulation.

[12]  Mark A. Hall,et al.  Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium. , 2004, Blood.

[13]  G. Veronesi,et al.  Assessing Tumor Angiogenesis , 2004, Cancer Research.

[14]  M. De Cicco,et al.  The prothrombotic state in cancer: pathogenic mechanisms. , 2004, Critical reviews in oncology/hematology.

[15]  R. Brook,et al.  Endothelial cell apoptosis in systemic lupus erythematosus: a common pathway for abnormal vascular function and thrombosis propensity. , 2004, Blood.

[16]  F. Ingegnoli,et al.  Circulating endothelial cells as a marker of ongoing vascular disease in systemic sclerosis. , 2004, Arthritis and rheumatism.

[17]  G. Lip,et al.  Assessment of endothelial damage in atherosclerotic vascular disease by quantification of circulating endothelial cells. Relationship with von Willebrand factor and tissue factor. , 2004, European heart journal.

[18]  Ricky T. Tong,et al.  Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer , 2004, Nature Medicine.

[19]  A. Blann Assessment of Endothelial Dysfunction: Focus on Atherothrombotic Disease , 2003, Pathophysiology of Haemostasis and Thrombosis.

[20]  L. Horstman,et al.  Endothelial microparticles released in thrombotic thrombocytopenic purpura express von Willebrand factor and markers of endothelial activation , 2003, British journal of haematology.

[21]  J. Folkman,et al.  Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells. , 2003, Cancer research.

[22]  R. Hebbel,et al.  Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. , 2003, Blood.

[23]  R. Kerbel,et al.  Maximum tolerable dose and low-dose metronomic chemotherapy have opposite effects on the mobilization and viability of circulating endothelial progenitor cells. , 2003, Cancer research.

[24]  E. Lee,et al.  Circulating numbers of endothelial progenitor cells in patients with gastric and breast cancer. , 2003, Cancer letters.

[25]  J. Freyssinet Cellular microparticles: what are they bad or good for? , 2003, Journal of thrombosis and haemostasis : JTH.

[26]  L. Naldini,et al.  Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells , 2003, Nature Medicine.

[27]  R. Jain,et al.  Role of bone marrow-derived cells in tumor angiogenesis and treatment. , 2003, Cancer cell.

[28]  Shahin Rafii,et al.  Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration , 2003, Nature Medicine.

[29]  Zvi Fuks,et al.  Tumor Response to Radiotherapy Regulated by Endothelial Cell Apoptosis , 2003, Science.

[30]  J. Isner,et al.  Stromal Cell–Derived Factor-1 Effects on Ex Vivo Expanded Endothelial Progenitor Cell Recruitment for Ischemic Neovascularization , 2003, Circulation.

[31]  Christie M. Orschell,et al.  Peripheral Blood “Endothelial Progenitor Cells” Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors , 2003, Circulation.

[32]  M. Endres,et al.  Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. , 2003, Circulation.

[33]  L. Horstman,et al.  Endothelial cells release phenotypically and quantitatively distinct microparticles in activation and apoptosis. , 2003, Thrombosis research.

[34]  Hung-Fat Tse,et al.  Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation , 2003, The Lancet.

[35]  T. Suda,et al.  Fibroblast growth factor receptor-1 is expressed by endothelial progenitor cells. , 2002, Blood.

[36]  Koichi Hattori,et al.  Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? , 2002, Nature Reviews Cancer.

[37]  Donald W Kufe,et al.  Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  M. Corada,et al.  A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability. , 2002, Blood.

[39]  M Gion,et al.  Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. , 2002, European journal of cancer.

[40]  S. Kirchner,et al.  Fludarabine induces apoptosis, activation, and allogenicity in human endothelial and epithelial cells: protective effect of defibrotide. , 2002, Blood.

[41]  S. Fucharoen,et al.  Increased circulating activated endothelial cells, vascular endothelial growth factor, and tumor necrosis factor in thalassemia , 2002, American journal of hematology.

[42]  S. Rafii,et al.  Efficient mobilization and recruitment of marrow-derived endothelial and hematopoietic stem cells by adenoviral vectors expressing angiogenic factors , 2002, Gene Therapy.

[43]  S. Rafii,et al.  Contribution of marrow-derived progenitors to vascular and cardiac regeneration. , 2002, Seminars in cell & developmental biology.

[44]  Vincenza Dolo,et al.  Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. , 2002, The American journal of pathology.

[45]  A. Tedgui,et al.  Circulating Microparticles From Patients With Myocardial Infarction Cause Endothelial Dysfunction , 2001, Circulation.

[46]  S. Rafii,et al.  Impaired recruitment of bone-marrow–derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth , 2001, Nature Medicine.

[47]  S. Fichtlscherer,et al.  Increase in Circulating Endothelial Progenitor Cells by Statin Therapy in Patients With Stable Coronary Artery Disease , 2001, Circulation.

[48]  T. Murohara,et al.  Mobilization of Endothelial Progenitor Cells in Patients With Acute Myocardial Infarction , 2001, Circulation.

[49]  A. Goldhirsch,et al.  Resting and activated endothelial cells are increased in the peripheral blood of cancer patients. , 2001, Blood.

[50]  S. Rafii,et al.  Vascular Endothelial Growth Factor and Angiopoietin-1 Stimulate Postnatal Hematopoiesis by Recruitment of Vasculogenic and Hematopoietic Stem Cells , 2001, The Journal of experimental medicine.

[51]  S. Homma,et al.  Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function , 2001, Nature Medicine.

[52]  S. Rafii,et al.  Vascular Trauma Induces Rapid but Transient Mobilization of VEGFR2+AC133+ Endothelial Precursor Cells , 2001, Circulation research.

[53]  E. Gunsilius,et al.  Correspondence re: M.L. George [correction of H.L. George] et al., Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging? Clin. Cancer Res., 6: 3147-3152, 2000. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[54]  M. Harmsen,et al.  Acute rejection before cytomegalovirus infection enhances von Willebrand factor and soluble VCAM-1 in blood. , 2000, Kidney international.

[55]  E. Raines,et al.  Endothelial cells of hematopoietic origin make a significant contribution to adult blood vessel formation. , 2000, Circulation research.

[56]  S. Eccles,et al.  Correlation of plasma and serum vascular endothelial growth factor levels with platelet count in colorectal cancer: clinical evidence of platelet scavenging? , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[57]  R Bicknell,et al.  Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. , 2000, Cancer research.

[58]  K. Pantel,et al.  In vitro differentiation of endothelial cells from AC133-positive progenitor cells , 2000 .

[59]  J. Freyssinet,et al.  Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. , 2000, Circulation.

[60]  S. Rafii,et al.  Expression of VEGFR-2 and AC133 by circulating human CD34(+) cells identifies a population of functional endothelial precursors. , 2000, Blood.

[61]  K. Pantel,et al.  In vitro differentiation of endothelial cells from AC133-positive progenitor cells. , 1999, Blood.

[62]  J. Isner,et al.  Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization. , 1999, Circulation research.

[63]  J. Isner,et al.  VEGF contributes to postnatal neovascularization by mobilizing bone marrow‐derived endothelial progenitor cells , 1999, The EMBO journal.

[64]  G. Grau,et al.  In vitro generation of endothelial microparticles and possible prothrombotic activity in patients with lupus anticoagulant. , 1999, The Journal of clinical investigation.

[65]  Hiroshi Takahashi,et al.  Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon , 1999, Nature Medicine.

[66]  Haruchika Masuda,et al.  Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization , 1999, Nature Medicine.

[67]  H. Shiku,et al.  Tissue Factor Expression and Metastatic Potential of Colorectal Cancer , 1998, Thrombosis and Haemostasis.

[68]  G. Bieler,et al.  Evidence for the involvement of endotheliai cell integrin αVβ3 in the disruption of the tumor vascuiature induced by TNF and IFN-γ , 1998, Nature Medicine.

[69]  E. Wayner,et al.  Circulating activated endothelial cells in sickle cell anemia. , 1997, The New England journal of medicine.

[70]  M. Lampugnani,et al.  Interendothelial junctions: structure, signalling and functional roles. , 1997, Current opinion in cell biology.

[71]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[72]  Takayuki Asahara,et al.  Isolation of Putative Progenitor Endothelial Cells for Angiogenesis , 1997, Science.

[73]  Lieve Moons,et al.  Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele , 1996, Nature.

[74]  M. Petri,et al.  Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[75]  G. Hair,et al.  In situ detection of tissue factor in vascular endothelial cells: Correlation with the malignant phenotype of human breast disease , 1996, Nature Medicine.

[76]  S. Tebbutt,et al.  Extrinsic-pathway activation in cancer with high factor Vlla and tissue factor , 1995, The Lancet.

[77]  F. Re,et al.  Inhibition of anchorage-dependent cell spreading triggers apoptosis in cultured human endothelial cells , 1994, The Journal of cell biology.

[78]  T. Luther,et al.  Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. , 1994, The Journal of clinical investigation.

[79]  J P Cazenave,et al.  Rapid Isolation of Human Endothelial Cells from Whole Blood Using S-Endo1 Monoclonal Antibody Coupled to Immuno-Magnetic Beads: Demonstration of Endothelial Injury after Angioplasty , 1992, Thrombosis and Haemostasis.

[80]  C. Esmon,et al.  Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. , 1990, The Journal of biological chemistry.

[81]  J. Denekamp,et al.  Endothelial proliferation in tumours and normal tissues: continuous labelling studies. , 1984, British Journal of Cancer.

[82]  R. D'Amato,et al.  Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. , 2005, Cancer cell.

[83]  G. Lip,et al.  Circulating endothelial cells: markers of vascular dysfunction. , 2005, Clinical laboratory.

[84]  E. Voest,et al.  Increased levels of viable circulating endothelial cells are an indicator of progressive disease in cancer patients. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[85]  G. Pruneri,et al.  Circulating endothelial cells as a novel marker of angiogenesis. , 2003, Advances in experimental medicine and biology.

[86]  Giovanni Martinelli,et al.  Continuous infusion of endostatin inhibits differentiation, mobilization, and clonogenic potential of endothelial cell progenitors. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[87]  R. Hebbel,et al.  Origins of circulating endothelial cells and endothelial outgrowth from blood. , 2000, The Journal of clinical investigation.

[88]  H. Verheul,et al.  Platelet and coagulation activation with vascular endothelial growth factor generation in soft tissue sarcomas. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[89]  A. Blann,et al.  HEMOSTASIS , THROMBOSIS , AND VASCULAR BIOLOGY Direct Evidence of Endothelial Injury in Acute Myocardial Infarction and Unstable Angina by Demonstration of Circulating Endothelial Cells , 1999 .

[90]  G. Bieler,et al.  Evidence for the involvement of endothelial cell integrin alphaVbeta3 in the disruption of the tumor vasculature induced by TNF and IFN-gamma. , 1998, Nature medicine.

[91]  E. Jaffe,et al.  Plasma from patients with idiopathic and human immunodeficiency virus-associated thrombotic thrombocytopenic purpura induces apoptosis in microvascular endothelial cells. , 1996, Blood.

[92]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[93]  G. Nicolson,et al.  Effects of chemotherapeutic drugs on platelet and metastatic tumor cell-endothelial cell interactions as a model for assessing vascular endothelial integrity. , 1985, Cancer research.

[94]  Identification and characterization of a very low density lipoprotein receptor–binding peptide from tissue factor pathway inhibitor that has antitumor and antiangiogenic activity , 2022 .