FF127ECEd01 - The Hallmarks of Cancer Angiogenesis 1 Tumor vasculature 2 What is angiogenesis(I De novo formation of blood vessels from endothelial

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1 The Hallmarks of Cancer Angiogenesis
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2 Tumor vasculature Tumor vasculature
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3 What is angiogenesis? (I) What is angiogenesis? (I) De novo formation of blood vessels from endothelial precursor cells (called angioblast). This vasculogenesis occurs mainly during embryogenesis. In the adult the vasculature is remarkably quiescent and angiogenesis occurs only rarely. Angiogenesis is involved in the turnover of tissues in the female reproductive system and in wound healing. Angiogenesis is the growth of new blood vessels from pre-existing vasculature by budding and sprouting of endothelial cells.
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4 What is angiogenesis? (II) Vasculogenesis angioblasts home from the bone of peripheral blood Into tumors Angiogenesis vascular network expansion by budding and bridging Lymphangiogenesis lymphatic vessels arround tumors drain interstitial fluid Intussusceptive growth insertion of interstitial tissue columns into lumen of pre-existing vessels
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5 Morphology of blood vessels • Vasculature is lined by a single layer of endothelial cells. • Endothelial cells form a simple squamous epithelium which rests on a basement membrane (collagen types I and IV, fibronectin, laminin, entactin and other non- collagen glycoproteins) • Endothelial cells + basement membrane= lamina intima
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6 Cross sections of breast cancer in Cross sections of breast cancer in mice mice A-B: green fluorescent lectin staining C: CD31 immunoreactivity by CY3 staining
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7 Ultrastructure Ultrastructure of a capillary of a capillary B: basement membrane E: endothelial cells P: pericytes
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8 Morphology of blood vessels Morphology of blood vessels Vasculature is lined by a single layer of endothelial cells. Endothelial cells form a simple squamous epithelium which rests on a basement membrane (collagen types I and IV, fibronectin, laminin, entactin and other non-collagen glycoproteins) Endothelial cells + basement membrane= lamina intima The lamina intima is surrounded by pericytes, smooth muscle cells or cardiomyocytes The endothelium in an adult has a surface area of > 1000 m2
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9 Vessel formation and maturation (I) Vessel formation and maturation (I) • The final stage of angiogenesis vessel assembly and maturation – stable vessel with blood flow – Recruitment of pericytes • Pericytes are recruited as local mesenchymal cells wich are stimulated by endothelial cells to differentiate into pericytes • Localized concentrations of PDGF are needed to ensure the pericytes are recruited to the outer layers of capillaries. Recruitment of pericytes towards endothelial cells is disrupted WT MT
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10 Vessel formation and maturation (II) Vessel formation and maturation (II) • The final stage of angiogenesis vessel assembly and maturation – stable vessel with blood flow – Recruitment of pericytes • Pericyte cells are related to smooth muscle cells • Pericytes secrete factors as TGF- β which stabilize endothelial cells and prevent their proliferation • Pericyte density is negatively correlated with the turnover rate of endothelial cells
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11 The wall of a blood vessel The wall of a blood vessel
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This note was uploaded on 05/28/2010 for the course WE MOBI000000 taught by Professor Geertberx during the Spring '10 term at Ghent University.

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FF127ECEd01 - The Hallmarks of Cancer Angiogenesis 1 Tumor vasculature 2 What is angiogenesis(I De novo formation of blood vessels from endothelial

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