Human cells secrete cancer-killing protein

Human cells are able to secrete a cancer-killing protein, scientists at the University of Kentucky's Markey Cancer Center have found.

Researchers led by Vivek Rangnekar, UK professor of radiation medicine, have determined that the tumor-suppressor protein Par-4, initially thought to be active only within cells expressing the Par-4 gene, is in fact secreted by most human and rodent cells and can target large numbers of cancer cells by binding to receptors on the cell surface.

This discovery, published today in the leading journal Cell, makes Par-4 a very attractive molecule for future research aimed at developing new cancer treatments.

"It was a pleasant surprise, when we noticed that Par-4 protein is secreted by cells," Rangnekar said. "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."

Funded by several grants from the National Institutes of Health, Rangnekar's study found that when the Par-4 molecule binds to its receptor GRP78 on the surface of a tumor cell, it triggers a biological process called apoptosis or "cell suicide." Consistent with previous research by Rangnekar's laboratory with intracellular Par-4, the newly discovered secreted Par-4 acts selectively against cancer cells, leaving healthy cells unharmed. Few other molecules are known to exhibit such selectivity.

One molecule, known as TRAIL, also exerts cancer-cell-specific effects. However, Rangnekar's most recent study discovered that apoptosis inducible by TRAIL is dependent upon extracellular Par-4 signaling via cell surface GRP78. Thus, the researchers conclude, Par-4 activates a novel pathway involving cell surface GRP78 receptor for induction of apoptosis. In other words, without Par-4, TRAIL lacks the ability to cause "cell suicide."

Rangnekar first discovered the Par-4 gene in 1993. In 2007, Rangnekar's team introduced the gene into a mouse embryo, creating a cancer-resistant "supermouse" that did not develop tumors. In fact, the mice possessing Par-4 actually live a few months longer than lab mice without the gene, indicating that Par-4 mice have no toxic side effects.

While Par-4 is not necessarily a "magic bullet" — it does not target every type of cancer cell — Rangnekar says it could play a major role in developing new combination treatment modalities for cancer patients. His hope is that the next generation of treatments will be even more effective than conventional treatments available today, with fewer and less severe side effects.

"I look at this research from the standpoint of how it can be developed to benefit the cancer patient, and that's what keeps us focused," Rangnekar said, discussing the potential of Par-4 in 2007. "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's a major breakthrough."

Rangnekar holds the Alfred Cohen, M.D., Endowed Chair in Oncology Research at the UK College of Medicine.

Source: University of Kentucky

   

• ArtflDgr - Jul 24, 2009
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  and if you look at the most recent stem cell work you will find that this is a supression loop. that is there is no such thing as a wait state in living. everything is a loop, since only a loop can determine a null is a nul and not a wait state.
  
  so cells secrete this and keep each other in the normal cellular wait state. when this changes
  
  try not to use biased terms like fail, bad, etc. its just a physical occurance, the outcome to us is bad, but may not be to the species as a whole in the long run. there is no reason to make such judgments within the work. one may use such a judgment to decide what work to look at as an impetus, but there you really trying to learn what happens, not divide arbitrary physical processes into two camps. at the cellular level the appearance or lack of par-4 is just a physical condition liek any other protein that is benificial, or harmful.
  
  in this way we have prevented ourselve the clarity that is common to physics.
  
  an example would be radiation. in physics it has no good or bad condition, but in biology it does. its mostly bad, but sometimes good, etc.. these are arbitrary value judgements that are contextual to our lives and outcomes, and has no bearing at the atomic level where these things interact.
  
  thats just how i see it, and its easier to see whats going on if one isnt constantly walking around stamping good and bad no processes whose good and bad is only in one context. (if a cancer puts out a benificial chemical, which many do, then what? does it get a good/bad proportional value?)
  
  got to go.. just thinking...
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