Secreted Tumor-Suppressor Protein Eyed as Potential Anticancer Drug

Cancer researchers have found that some types of both normal and cancerous cells growing in tissue culture secrete the Par-4 tumor-suppressor protein, the potential basis for a highly selective anticancer drug.

Par-4 inhibits tumor growth by initiating the process of apoptosis in cancer cells that express the specific glucose-regulated protein-78 (GRP78) surface receptor. While it had been known that Par-4 protein was present in cells that contain the Par-4 gene, an article in the July 23, 2009, issue of the journal Cell was arguably the first to report that some types of cells secrete Par-4. Not only was Par-4 secreted spontaneously, short exposure to endoplasmic reticulum (ER) stress-inducing agents further increased its cellular secretion. Secreted Par-4 was shown to act in the same fashion as the endogenous protein by triggering apoptosis in cancer cells while leaving normal cells unharmed.

"It was a pleasant surprise, when we noticed that Par-4 protein is secreted by cells,” said senior author Dr. Vivek Rangnekar, professor of radiation medicine at the University of Kentucky (Lexington, USA). "This new finding means it is not necessary to make genetic modifications, or to employ recombinant viruses, to deliver the Par-4 gene to cancer cells, and it significantly expands the potential applications of Par-4 to selectively kill cancer cells. I look at this research from the standpoint of how it can be developed to benefit the cancer patient, and that is what keeps us focused,” said Dr. Rangnekar. "The pain that cancer patients go through--not just from the disease, but also from the treatment--is excruciating. If you can treat the cancer and not harm the patient, that is a major breakthrough.”

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