Is Angiopoietin-2 Necessary for the Initiation of Tumor Angiogenesis?
| Autor: | Juha Lauren, Yuji Gunji, Kari Alitalo |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
0303 health sciences
Pathology medicine.medical_specialty Endothelium Angiogenesis Blood flow Biology 3. Good health Pathology and Forensic Medicine Extracellular matrix Endothelial stem cell 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Vasculogenesis 030220 oncology & carcinogenesis cardiovascular system medicine Wound healing 030304 developmental biology Blood vessel |
| Zdroj: | The American Journal of Pathology. 153:1333-1339 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/s0002-9440(10)65717-3 |
| Popis: | Almost all functional cells are located within 30 μm of a blood capillary. Acute changes in blood flow are regulated in response to tissue needs by changes in the constriction level of blood vessels, 1 whereas long-term regulation of tissue perfusion is achieved by growth of new blood vessels or by vascular regression. 2 Physiological angiogenesis is limited to wound healing and changes in female reproductive organs during the menstrual cycle and pregnancy but blood vessels maintain their ability to grow and regress throughout life. Changes in the vasculature occur in association with many pathological processes, such as ocular neovascularization, inflammatory diseases, and cancer. 3 The concept that solid tumor growth depends on angiogenesis is well established. 4 Indeed, tumor size is restricted to a few cubic millimeters if it is not able to attract new blood vessels. The primitive embryonic vasculature is laid down by vasculogenesis, 5 which involves in situ differentiation of endothelial cells (ECs) from mesodermal precursors and their organization into a primary vascular plexus. In adults, all new blood vessels appear to be formed by angiogenesis, which is based on sprouting of blood vessels from existing ones or on intussusceptive growth involving in situ remodeling of the vessels by protruding interstitial tissue columns. In embryos, some developing organs including the brain and kidneys are vascularized by angiogenesis. The initiation of blood vessel growth involves focal reduction of intercellular interactions and interactions between the cells of the blood vessel and the surrounding extracellular matrix (ECM). This is associated with a loss of pericytes (PCs) and possibly of smooth muscle cells (SMCs) from the existing vessels. 2 Many angiogenic factors have been shown to be mitogenic and chemoattractive for ECs. The ECs have been shown to distort malleable substrata in a process called traction 6,7 and the reorganized ECM may facilitate the formation of complex weblike EC structures. Formation of functional blood vessels requires remodeling of this EC meshwork. Initiation of blood flow enables adaptation to changing blood and oxygen pressure conditions and further remodeling of the vascular network. 8 The maturation of newly formed vessels involves the accumulation of a basal lamina and tightly associated PCs or SMCs on the abluminal side. Although many phases of vessel growth overlap, this classification shows that complex orchestration is required in order for angiogenesis to proceed. Numerous substances can trigger the angiogenic process by causing a reprogramming of cells in the blood vessels 9 and these responses are beginning to be elucidated. In this issue of The American Journal of Pathology, Stratmann et al 10 report their novel finding that the angiopoietin-2 (Ang-2) signaling molecule is up-regulated in a spotlike fashion in the endothelium of growing blood vessels in glioblastoma. The authors also show that angiopoietin-1 (Ang-1), a related signaling molecule, is secreted from tumor cells and that Tie-2, a receptor for both Ang-1 and Ang-2, is up-regulated in the endothelium of vessels undergoing angiogenesis. |
| Databáze: | OpenAIRE |
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