Summary
It has been known for over a century that blood coagulation and fibrinolysis pathways
are activated systemically in patients with malignancy. Recent studies have revealed
evidence for two distinct pathways of interaction between tumor cells and the host
coagulation mechanism that include production of either initiators of thrombin formation
or expression of plasminogen activators by the tumor cells in situ within intact tumor tissue. Studies in specific in vitro and animal models of malignancy
have implicated either tumor cell procoagulants or urokinase in mechanisms of tumor
cell proliferation, invasion, and metastasis. We have formulated a classification
of human tumor types based on detection of components of either of these pathways
in situ. Type I tumors are those in which the tumor cells are associated with an intact coagulation
pathway that leads to thrombin formation at the tumor periphery but in which the tumor
cells lack urokinase. Type II tumors are those in which the tumor cells express urokinase
but lack an associated coagulation pathway leading to thrombin formation. Type III
tumors are those that express neither of these pathways, or exhibit some other pattern
of interaction. Evidence suggests that anticoagulant therapy is capable of ameliorating
the clinical course of a procoagulant tumor type namely, small cell carcinoma of the
lung. This approach may be effective in other type I tumors. Clinical trials of agents
capable of inhibiting urokinase-initiated proteolysis are required to clarify cause/effect
relationships in urokinase-expressing tumors. Exploration of the coagulation-cancer
interaction holds considerable promise for imaginative new approaches to cancer treatment
that are not only relatively nontoxic and low cost, but also effective because they
may interrupt fundamental mechanisms of malignant growth control.
Keywords
Blood coagulation - cancer - thrombin - urokinase
