Contribution of Endothelial Progenitor Cells to the Angiogenic Process (original) (raw)
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Cytometry Part A, 2008
Until recently, tumor vascularization was thought to occur exclusively through angiogenesis. However, recent studies using different animal models of cancer suggested the importance of bone marrow-derived endothelial progenitor cells (EPCs) (i.e. postnatal vasculogenesis) in tumor vascularization and growth. EPCs are present in the peripheral blood, their levels are increased in response to certain signals/cytokines, and they home into the neovascular bed of malignant tissues. Furthermore, at the clinical level, evidence is emerging that changes in EPC levels might predict the efficacy of anticancer drug combinations that include antiangiogenic agents. On the basis of these observations, EPCs have attractive potential diagnostic and therapeutic applications for malignant diseases. In this paper, we review biological features of EPCs and speculate on the utility of these progenitor cells for medical oncology. ' 2007 International Society for Analytical Cytology
Genes & …, 2007
. However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with ␣-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis.
Role of endothelial progenitor cells in cancer progression
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, 2014
Tumor-associated neovasculature is a critical therapeutic target; however, despite significant progress made in the clinical efficacy of anti-vessel drugs, the effect of these agents remains transient: over time, most patients develop resistance, which inevitably leads to tumor progression. To develop more effective treatments, it is imperative that we better understand the mechanisms involved in tumor vessel formation, how they participate to the tumor progression and metastasis, and the best way to target them. Several mechanisms contribute to the formation of tumor-associated vasculature: i) neoangiogenesis; ii) vascular co-option; iii) mosaicism; iv) vasculogenic mimicry, and v) postnatal vasculogenesis. These mechanisms can also play a role in the development of resistance to anti-angiogenic drugs, and could serve as targets for designing new anti-vascular molecules to treat solid as well as hematological malignancies. Bone marrow-derived endothelial progenitor cell (EPC)-mediated vasculogenesis represents an important new target, especially at the early stage of tumor growth (when EPCs are critical for promoting the "angiogenic switch"), and during metastasis, when EPCs promote the transition from micro-to macro-metastases. In hematologic malignancies, the EPC population could be related to the neoplastic clone, and both may share a common ontogeny. Thus, characterization of tumor-associated EPCs in blood cancers may provide clues for more specific anti-vascular therapy that has both direct and indirect anti-tumor effects. Here, we review the role of vasculogenesis, mediated by bone marrowderived EPCs, in the progression of cancer, with a particular focus on the role of these cells in promoting progression of hematological malignancies.
Involvement of endothelial progenitor cells in tumor vascularization
Microvascular Research, 2010
The generation of new microvasculature progresses by the process of angiogenesis, which involves the invasion and proliferation of endothelial cells from existing blood vessels into the local environment. In recent years, de novo generation of endothelial cells from circulating or local precursor endothelial cells is thought to also contribute to the neovasculature, a process that is referred to as vasculogenesis. In the adult, endothelial progenitor cells (EPC) are believed to be recruited from the bone marrow, migrate to sites requiring neovascularization and participate in the assembly of newly-forming blood vessels. A growing number of studies report that EPC participate in tumor progression and influence the efficacy of anticancer chemotherapeutics, and thus are attractive targets for cancer treatments. However, recent evidence calls into question the ability of marrow-derived EPC to act as a bona fide precursor for adult vasculogenesis. This review focuses on studies reporting or precluding the importance of EPC in tumor vasculogenesis. The putative sources of these cells and difficulties associated with their detection are discussed.
Circulating Endothelial Progenitor Cells
New England Journal of Medicine, 2005
Angiogenesis research investigates the formation of new blood vessels in wound healing, tumour growth and embryonic development. Circulating, bone marrow-derived endothelial progenitor cells (EPCs) were first described 8 years ago, yet the exact nature of these endothelial precursor cells remains unclear. The contributions of circulating EPCs to angiogenesis in tumours, ischaemic injury and other diseases as well as their usefulness in the repair of wounded hearts and limbs remain under intense investigation.
Endothelial progenitor cells do not contribute to tumor endothelium in primary and metastatic tumors
International Journal of Cancer, 2009
Despite extensive research, the contribution of bone‐marrow‐derived endothelial progenitor cells (BM‐EPC) to tumor angiogenesis remains controversial. In previous publications, the extent of incorporation of BM‐EPCs into the endothelial cell (EC) layer in different tumor models has been reported as significant in some studies but undetectable in others. Here, we studied the differentiation of BM‐EPCs and its contribution to tumor vessels in experimental and spontaneous lung metastasis (B16 melanoma and prostate carcinoma), in an autochthonous transgenic model of prostate tumorigenesis, in orthotopically implanted lung tumors [Lewis lung carcinoma (LLC)], in heterotopic subcutaneous models (LLC and C1 prostate carcinoma) growing in green fluorescent protein (GFP)‐expressing bone marrow (BM) chimeras. Immunofluorescence was performed with a set of endothelial and hematopoietic markers and confocal microscopy was used to generate 3D reconstruction images. By performing rigorously condu...
Stem Cell Reviews, 2008
Tumor growth and metastasis need new vessel formation by angiogenesis provided by mature endothelial cells and postnatal vasculogenesis provided by endothelial progenitor cells (EPCs). Emerging data suggest a coordinated interaction between EPCs and hematopoietic progenitor cells (HPCs) in these processes. The complexity of the mechanisms governing the new vessel formation by postnatal vasculogenesis has increased by new evidence that not only bone marrow derived EPCs and HPCs seem to be involved in this process but also local progenitors residing within the vascular wall are mobilized and activated to new vessel formation by tumor cells. This review attempts to bring these systemic and local players of postnatal vasculogenesis together and to highlight their role in tumor growth and mestastasis.
Circulating endothelial cells as biomarkers for angiogenesis in tumor progression
2009
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