Molecular mechanisms of tumor angiogenesis and tumor progression.
The formation of new blood vessels (angiogenesis) is crucial for the growth and persistence of primary solid tumors and their metastases. Furthermore, angiogenesis is also required for metastatic dissemination, since an increase in vascular density will allow easier access of tumor cells to the circulation. Induction of angiogenesis precedes the formation of malignant tumors, and increased vascularization seems to correlate with the invasive properties of tumors and thus with the malignant tumor phenotype. In the last few years, the discovery and characterization of tumor-derived angiogenesis modulators greatly contributed to our understanding of how tumors regulate angiogenesis. However, although angiogenesis appears to be a rate-limiting event in tumor growth and metastatic dissemination, a direct connection between the induction of angiogenesis and the progression to tumor malignancy is less well understood. In this review, we discuss the most recent observations concerning the modulation of angiogenesis and their implications in tumor progression, as well as their potential impact on cancer therapy.
Research Institute of Molecular Pathology, Vienna, Austria.
U
U
Cavallaro
G
G
Christofori
D043925:Angiogenesis Inducing Agents / Q000502:physiology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D043168:Angiostatins; D000818:Animals; D003094:Collagen / Q000502:physiology / Q000627:therapeutic use; D018450:Disease Progression; D043169:Endostatins; D016228:Endothelial Growth Factors / Q000502:physiology; D006801:Humans; D008222:Lymphokines / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000187:drug effects / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply*; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D010446:Peptide Fragments / Q000502:physiology / Q000627:therapeutic use; D010958:Plasminogen / Q000502:physiology / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects / Q000502:physiology; D042787:Receptor, TIE-2; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D043169:Endostatins; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2