No grip, no growth: the conceptual basis of excessive proteolysis in the treatment of cancer.
The formation of new bloodvessels, called angiogenesis, is critical for a tumour to grow beyond a few mm(3) in size. A provisional matrix promotes endothelial cell adhesion, migration, proliferation and survival. Synthesis and degradation of this matrix closely resemble processes that occur during coagulation and fibrinolysis. Degradation of the matrix and fibrinolysis are tightly controlled and balanced by stimulators and inhibitors of the plasminogen activation system. Here we give an overview of these processes during tumour progression. We postulate a novel way to inhibit angiogenesis by removal of the matrix through specific and localised overstimulation of the plasminogen activation system.
Reijerkerk
A
A
Laboratory of Medical Oncology, Department of Internal Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
Voest
E E
EE
Gebbink
M F
MF
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D043168:Angiostatins; D000970:Antineoplastic Agents / Q000627:therapeutic use; D025901:Carboxypeptidase B2; D002268:Carboxypeptidases / Q000502:physiology; D003094:Collagen / Q000627:therapeutic use; D043169:Endostatins; D006801:Humans; D008239:Lysine / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000473:pathology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010446:Peptide Fragments / Q000627:therapeutic use; D010958:Plasminogen / Q000627:therapeutic use; D010960:Plasminogen Activators / Q000502:physiology; D015912:Thrombolytic Therapy / Q000379:methods; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D008239:Lysine