Israeli scientists clone gene tied to spread of cancer

JERUSALEM — Researchers in Rehovot and Jerusalem have discovered and cloned a human gene responsible for the production of an enzyme that plays a major role in the spread of tumor cells.

They have also produced a genetically engineered version of this crucial enzyme.

The achievement is expected soon to play a major role in predicting which secondary tumors would be the most aggressive and would therefore require more powerful treatment.

The breakthrough could also lead to the development of enzyme inhibitors that could prevent tumor cells from proliferating, and of drugs for other diseases.

An application for patenting the recombinant enzyme and the gene code is in the process of being filed in the United States by researchers at InSight, a 3-year-old company in Rehovot, and by the tumor biology research unit, headed by Professor Israel Vlodavsky, a cell biologist at Hadassah-University Hospital in Jerusalem's Ein Kerem, who received its 1997 Outstanding Scientist Award.

News of the discovery was published Sunday in the Hed Hadassah newsletter. It is expected to be presented by the researchers at a June conference in the United States.

More than half of newly diagnosed cancer patients have secondary tumors, or metastases, which are often undetectable and can be fatal. Virtually all deaths from cancers of the colon, breast and many other organs are caused not by the primary tumor but by its offshoots elsewhere in the body.

Malignant cells usually invade blood vessels and pass into the extracellular matrix. Vlodavsky's work, which began 15 years ago, proved that tumor cells' ability to invade their surroundings depends on the activity of a cellular enzyme called heparanase, which breaks down a main component of the vascular wall called heparan sulfate.

Compounds that inhibit heparanase were found to inhibit the spread of metastasis in lab animals. The gene was found to be inactive in healthy people. In cancer patients, it "wakes up." The enzyme is especially prominent in people with aggressive cancers.

InSight molecular biologist Dr. Dror Melamed and Vlodavsky said Sunday that their work has paved the way for the development of molecular probes and antibodies for the early detection of tiny metastases of tumor cells in plasma, urine and other tissues and fluids. Working with the genetically engineered enzyme, the researchers believe they can develop heparanase inhibitors to halt the ability of secondary tumor cells and activated lymphocytes to break out of blood vessels and reach their target organs.

The discovery fits in well with the booming study of tumor angiogenesis — the growth of new blood vessels around the tumor that supply it with oxygen and nutrients, which makes possible the growth and spread of cancer.