In contrast to asTF, flTF was demonstrated to be the major source of procoagulant activity in cancer settings (8).
flTF was also found to induce angiogenesis in cancer (13, 30).
The Influence of asTF and flTF on Cancer Cell Proliferation and Tumor Growth
In vitro, blocking of flTF had no detectable impact on MDA-MD-231 cell proliferation (30).
In contrast to flTF, asTF was shown to promote cell proliferation in vitro as well as tumor growth in vivo (2, 10, 12, 21).
flTF was also found to affect cancer cell migration.
flTF, which is highly expressed in several types of cancer, is involved in cancer-related thrombosis, tumor growth, and metastasis (2-4, 8, 12, 13).
Substantiating this, inhibition of direct flTF:FVIIa signaling by monoclonal anti-flTF antibody 10H10 reduced tumor growth in aggressive breast cancer, whereas inhibition of TF-induced coagulation by monoclonal anti-flTF antibody 5G9 had only a minimal effect (30).
showed that inhibition of flTF by 10H10 effectively suppressed breast cancer tumor growth and metastasis in vitro and in vivo (30).
Taken together, recent antitumor strategies targeting flTF or flTF-mediated PAR-2 signaling show promising results but need further evaluation, especially in clinical studies, to assess potential benefits as well as to detect undesirable side effects.
In contrast to flTF, asTF was found to mediate its proangiogenic activity independently of PAR-2 via integrins, such as integrin [alpha]v[beta]3 (10, 24).