Protein Identified in Fast-Metastasizing Tumors

Researchers have discovered a protein that may explain why tumors in a low-oxygen environment are more lethal.

The findings, published April 27, 2006, in the journal Nature, revealed that tumors that are hypoxic (low in oxygen) make a protein called lysyl oxidase that helps the tumor metastasize to other organs. Lysyl oxidase (LOX), could be a good target for future cancer therapies, according to the researchers.

"All tumors have the potential to spread,” said lead author Amato Giaccia, M.D., professor of radiation oncology from the Stanford University School of Medicine (CA, USA). "A low-oxygen environment dials up that potential, and now we know why.”

Hypoxia is caused when the supply of oxygen from the bloodstream cannot meet demand from body tissues and tumors. Hypoxic tumors can be found in many areas of the body. For this study, the researchers evaluated both breast tumors and head and neck tumors. In each case, patients whose tumors produced high levels of LOX were more apt to have tumors that metastasize and to die of the disease.

To answer the question as to whether blocking LOX could also slow the cancer's spread, the researchers grew human tumors that produced high levels of LOX in mice. Using three different methods of blocking LOX production, they found that the tumors were less likely to spread than tumors producing LOX unimpeded.

According to Dr. Giaccia, blocking LOX in patients with hypoxic tumors has great potential as a new therapy. He added that there are several ways of determining whether a tumor is hypoxic and therefore likely to be producing LOX. Furthermore, one of the methods used to block LOX in mice was an antibody, the same type of protein as HER2/Neu, which has drastically improved outcomes in individuals with some types of breast tumors.

A therapy that specifically targets tumors producing LOX would be especially promising given that these are frequently among the most lethal cancers. Dr. Giaccia reported that trials in humans could begin as soon as 2009. The group is now looking at the relationship between LOX production and hypoxia in other types of tumors including colon and lung.



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Stanford University School of Medicine