Hybrid Toxin Stops Bone Cancer by Targeting VEGF Receptors

Cancer researchers have described the role of vascular endothelial growth factor (VEGF) in the process of tumor metastasis from tissues into bone.

Investigators at the University of Texas M. D. Anderson Cancer Center (Houston, USA) implanted human prostate cancer cells, which are highly metastatic to bone, directly into the leg bone marrow of experimental mice in order to simulate bone metastasis.

To study the role of VEGF, which many types of cancers produce in order to promote formation of new blood vessels, the investigators created a hybrid molecule (VEGF121/rGe) by fusing the smallest of VEGF proteins (VEGF 121) to a genetically engineered toxin, gelonin. Cells with VEGF receptors would bind this molecule only to be killed when the toxin was released into the cytoplasm.

The mice were treated one week after tumor implantation with five staggered doses of VEGF121/rGe delivered through intravenous injections. Results published in the November 15, 2006, issue of Cancer Research revealed that half of the treated animals did not develop any bone tumors. The investigators were not sure why all the mice were not protected and speculated that perhaps the treatment was given too long after tumor implantation.

The action of VEGF121/rGel seemed to be directed towards two different types of VEGF receptors. This theory emerged because it both prevented the bone destruction needed for the cancer to spread as well as inhibiting blood-vessel growth to the metastasized tumor.

Senior author Dr. Michael G. Rosenblum, professor of oncology at the University of Texas M. D. Anderson Cancer Center, said, "The fact that this form of VEGF targeting works on different cell receptors in blood vessels and in bone cells is a unique finding that could be clinically significant, not only to treating cancer but other bone disorders. In the least, this study helps us understand more about how VEGF operates inside the body and how it is involved in bone remodeling.”



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University of Texas M. D. Anderson Cancer Center