Fibrinogen facilitates the anti-tumor effect of nonnative endostatin.
Endostatin is a potent inhibitor of tumor angiogenesis. Interestingly, nonnative endostatin also exhibits an anti-tumor effect, which remains a mystery so far. Here, we show that intravenous injection of nonnative endostatin results in tumor inhibition effect. Soluble and active endostatin is isolated from human blood after the addition of nonnative endostatin in vitro. By fractionation of the whole blood, we surprisingly identify fibrinogen specifically binding to and inhibiting the aggregation of nonnative endostatin. Moreover, the anti-tumor activity of nonnative endostatin is substantially impaired in fibrinogen-deficient mice. Our studies demonstrate that fibrinogen facilitates the anti-tumor effect of nonnative endostatin, which also provides new insights into the novel physiological function of fibrinogen.
Tang
Huadong
H
Cancer Biology Laboratory, Department of Biological Sciences and Biotechnology, Tsinghua University, Qinghua Yuan 1, Beijing 100084, PR China.
Fu
Yan
Y
Lei
Qingxin
Q
Han
Qing
Q
Ploplis
Victoria A
VA
Castellino
Francis J
FJ
Li
Ling
L
Luo
Yongzhang
Y
D020533:Angiogenesis Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D043169:Endostatins / Q000378:metabolism / Q000494:pharmacology*; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D005340:Fibrinogen