The heparins and cancer.
Heparin, and particularly low molecular weight heparin, is widely used for the treatment of patients with deep vein thrombosis (DVT) and the prevention of DVT that commonly accompanies malignancy. Malignant growth has also been linked experimentally to the function of heparin-like glycosaminoglycans (HLGAGs). In addition to the voluminous general literature on this subject, the heparin-cancer link has been the theme of at least three entire journal issues in recent months. These include the June 15, 2001 issue of Thrombosis Research, the November 2001 Supplement to Haemostasis, and the February 2002 issue of Seminars in Thrombosis and Hemostasis. Previous reviews have documented the historical development of this link that includes evidence from basic biochemistry and cell biology, studies in experimental animal model systems, and clinical trials. This concise review updates recent basic and clinical data on the heparin-cancer link that clarify mechanisms by which HLGAGs regulate the malignant behavior of cells. Electronic access to information that is increasing geometrically has become indispensable. Evidence for control of tumor cell growth by heparin-binding growth factors, tumor cell invasion by heparin-inhibitable enzyme systems, tumor cell metastasis by heparin-binding cell surface selectins, tumor angiogenesis, and tumor matrix formation related to deposition of fibrinogen/fibrin provides a secure theoretical foundation for systematic testing of this class of compounds in patients with cancer. HLGAGs may be a fundamental intermediate in the abnormal growth regulation characteristic of neoplasia that is susceptible to targeted intervention.
Zacharski
Leo R
LR
The Department of Veterans Affairs Medical Center, White River Jct., Vermont 05009, USA. leo.r.zacharski@dartmouth.edu
Loynes
James T
JT
D000925:Anticoagulants / Q000627:therapeutic use*; D015897:Comorbidity; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006497:Heparan Sulfate / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D006497:Heparan Sulfate