Urokinase-targeted recombinant bacterial protein toxins — a rationally designed and engineered anticancer agent for cancer therapy |
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Authors: | Yizhen Liu and Shi-Yan Li |
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Institution: | (1) Department of Biomedical Sciences, Colorado State University, Font Collins, CO 80523, USA;(2) Cancer Research Institute of Scott & White, Temple, TX 76502, USA |
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Abstract: | Urokinase-targeted recombinant bacterial protein toxins are a sort of rationally designed and engineered anticancer recombinant
fusion proteins representing a novel class of agents for cancer therapy. Bacterial protein toxins have long been known as
the primary virulence factor(s) for a variety of pathogenic bacteria and are the most powerful human poisons. On the other
hand, it has been well documented that urokinase-type plasminogen activator (uPA) and urokinase plasminogen activator receptor
(uPAR), making up the uPA system, are over-expressed in a variety of human tumors and tumor cell lines. The expression of
uPA system is highly correlated with tumor invasion and metastasis. To exploit these characteristics in the design of tumor
cell-selective cytotoxins, two prominent bacterial protein toxins, i.e., the diphtheria toxin and anthrax toxin are deliberately
engineered through placing a sequence targeted specifically by the uPA system to form anticancer recombinant fusion proteins.
These uPA system-targeted bacterial protein toxins are activated selectively on the surface of uPA system-expressing tumor
cells, thereby killing these cells. This article provides a review on the latest progress in the exploitation of these recombinant
fusion proteins as potent tumoricidal agents. It is perceptible that the strategies for cancer therapy are being innovated
by this novel therapeutic approach. |
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Keywords: | urokinase-type plasminogen activator (uPA) diphtheria toxin anthrax toxin recombinant fusion proteins cancer therapy |
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