ABSTRACT
There is now considerable evidence that the blood coagulation system plays an important
role in the biology of malignant tumors. This evidence has been derived from a combination
of clinical, biochemical, histological, and pharmacological observations that point
to the possibility of favorably affecting the course of malignant disease with agents
that interfere with blood coagulation pathways. For a number of years our laboratory
has used experimental models of blood-borne metastasis to study the events that follow
the introduction of procoagulant-bearing tumor cells into the circulating blood. This
article summarizes our experience with these models, which suggests that intravascular
coagulation is a necessary prelude to lung tumor formation and that interruption of
coagulation pathways in various ways may be an effective antimetastatic strategy.
We have shown that anticoagulation with commonly used agents such as unfractionated
heparin and warfarin (Coumadin) prevent tumor formation by limiting the ability of
tumor cells to be retained in the pulmonary microvasculature. Binding of fibrin-coated
tumor cells to activated platelets is essential for this retention and, therefore,
treatment with potent antiplatelet agents such as abciximab is also effective. The
predominant tumor procoagulant is tissue factor (TF), and direct targeting of this
protein with concanavalin A, monoclonal antibodies, and tissue factor pathway inhibitor
(TFPI) has provided compelling evidence that TF is an important determinant of tumor
seeding in these experimental models. Collectively, our data provide strong support
for the concept that some form of anticoagulant therapy would be a useful adjunct
to existing cancer treatments.
KEYWORD
Cancer - metastasis - tissue factor - anticoagulants - Coumadin - heparin - tissue
factor pathway inhibitor - treatments
