Suicidal progenitors attack metastases
Metastatic tumors depend on the recruitment of new blood vessels to survive and thrive in an organism. Beltinger and colleagues have designed a potential cancer therapy that manipulates the very process required for metastatic tumor growth: the recruitment of embryonic endothelial progenitor cells (eEPCs) during new blood vessel development. The authors genetically modify eEPCs to express an inducible 'suicide' gene (cytosine deaminase–uracil phosphoribosyl transferase, which converts a prodrug into the cytotoxic compound 5-fluorouracil) and then inject the eEPCs into the tail vein of mice containing previously established metastases. Consistent with the role of endothelial cells, eEPCs were found to home preferentially to poorly vascularized metastatic tumors in the lung. Induced expression of the suicide gene resulted in tumor cell death via a bystander effect, leading to a significant increase in mouse survival. Interestingly, eEPCs were found to lack expression of major histocompatibility complex 1 antigens and to resist natural killer cell–mediated death, both beneficial properties for evading immunogenic responses, suggesting that eEPCs may be useful as general purpose vectors for gene therapy. (Cancer Cell 5, 477–488, 2004) NC
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