Antimetastatic agents. II. Summary of the interactions of tumor cells with blood coagulation factors, platelets, fibrinolytic factors, and inflammatory cells and their soluble mediators: potential for therapeutic interventions.
Although not reviewed during this session of the Workshop, other reactions in the hemostatic pathways are relevant to tumor-host cell interactions, are potential targets for antimetastatic agents, and are therefore included in Figure 1 and Table 1. For example, elsewhere in this issue of Seminars Loskutoff reviews the recent evidence for the importance of naturally occurring plasminogen activator inhibitors in the regulation of fibrinolysis. Since tumor cells may contain both tissue plasminogen activator and a urokinase-like plasminogen activator, the balance between tumor-mediated fibrin formation and fibrinolysis becomes an important issue in assessing antimetastatic treatment protocols. The relationship of the fibrinolytic pathways to metastasis has been reviewed recently by Dano and colleagues. Clearly, no single therapeutic approach designed to inhibit only one of these complicated interactions between tumor cells and host defense mechanisms is likely to be successful. However, each of the pathways illustrated (Fig. 1) and each of the theoretical steps in the metastatic cascade (Table 1) must be considered in the design of new strategies for the use of antimetastatic agents.
Rickles
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FR
Department of Medicine, University of Connecticut School of Medicine, Farmington 06032.
Hancock
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WW
D000925:Anticoagulants / Q000627:therapeutic use; D001779:Blood Coagulation Factors / Q000502:physiology*; D001792:Blood Platelets / Q000502:physiology*; D005342:Fibrinolysis; D006801:Humans; D007167:Immunotherapy; D007249:Inflammation; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use
D000925:Anticoagulants; D001779:Blood Coagulation Factors; D010975:Platelet Aggregation Inhibitors