FortyYear Cancer Foe

April 6, 2007
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GRAND RAPIDS — For 40 years, George Vande Woude, Ph.D., director of Van Andel Research Institute, has been trying to hunt down the cause of cancer, and he has never wavered from his mission.

Along the way, he has become one of the world’s most renowned experts in molecular oncology, garnering numerous honors and accolades. His research into the biochemical pathways underlying tumor growth and metastasis continues today at VARI’s Laboratory of Molecular Oncology.

When Vande Woude was an undergraduate, the two main schools of thought were that cancer was caused by viruses and the environment. Viruses were known to be associated with cancer, but it wasn’t clearly understood how, Vande Woude recalled. Emphasis in the 1970s was on the viruses that caused cancer, known as retroviruses. 

According to Vande Woude, the retrovirus had a very unique cycle; it would infect a cell and insert its genetic information into the cell. Sometimes it would insert itself into an oncogene — a gene that causes normal cells to change into cancerous tumor cells. When that happened, the retrovirus would “turn the gene on”; that was one of the ways viruses were causing cancer, he noted.

The real breakthroughs, however, came when scientists began studying the genetics of cancers, Vande Woude said. What scientists discovered was that different environmental factors, such as carcinogens and viruses, were perturbing the genetic information of the host.

There are 30,000 genes in the human genome. Each one has multiple functions, but there are only some that can cause cancer if they are inappropriately expressed, he said.

In 1984, while serving as a laboratory director at the National Cancer Institute’s Frederick Cancer Research and DevelopmentCenter Vande Woude and his team of scientists identified the human Met oncogene. Met is a transmembrane protein found in many different types of human cells. Vande Woude’s lab was the first to show that increased expression of the Met protein occurs in human tumors. Met research has been the primary focus of his work ever since then.

Thanks in large part to Vande Woude’s contributions to cancer biology, Met is universally recognized today as playing a key role in both normal and abnormal biological processes development, such as cancer metastases. His research on the Met protein has helped to stimulate scientists worldwide to study its role in cancer and to develop ways for treating those cancers expressing Met.

Met is a “receptor,” a class of gene that sits on the surface of a cell and has both external and internal portions. The external portion can sense the environment, including when something binds to it. The internal portion of Met sends a signal to tell the cell what to do as a result; it relays signals that “turn on” a cell’s internal machinery.

Met, he explained, causes certain cells to grow and divide; it also causes cells to scatter or migrate. Tumor cells that have both characteristics can’t be stopped or controlled by natural processes and tend to become highly malignant, he observed. 

Vande Woude and his colleagues were the first to show that inappropriate Met expression occurs in human tumors and that Met’s intracellular signaling can render cells tumorigenic and metastatic. When Met is inappropriately expressed, he explained, the expression gives a tumor the ability to survive against oxygen deprivation, as well as the ability to proliferate and migrate.

A couple of years ago, he and his VARI colleagues began studying how Met is involved in different kinds of cancer. They found that Met is involved in a number of cancers — including brain tumors, breast cancer, carcinomas, prostate cancer and musculoskeletal sarcomas — and that a high expression of Met correlates with poor prognosis.

Vande Woude’s lab, in fact, put together the Met and Cancer Reference Chart, which is posted on VARI’s Web site ( It lists all the cancers and notes whether Met is expressed in each particular cancer; whether there is a poor prognosis; whether any mutations have been found; and whether there are any therapeutic treatments available.

“Mutations are really compelling evidence that Met is involved, because you have a normal molecule, then a change occurs that associates with the tumor,” Vande Woude elaborated. “You can take that change and show now that that molecule, by itself, put into a cell, will cause that cell to become tumorigenic. It’s really important, and that’s one of the things we’re really good at.”

He said his lab is also good at putting molecules into a cell that will knock out the Met expression. That “knockout punch” stops the tumor from growing.

“The most important validation is showing that you have a drug that blocks or inhibits the activity, and then showing that it has an effect in patients,” he pointed out.

Vande Woude said he believes the Met and Cancer Reference Chart has been very useful for drug companies that are trying to figure out what kind of cancer to target. His lab has recently been involved with many companies that are making drugs, and over the years his staff has made many assays to measure selected activities that come from signaling from the Met receptor, he said.

Met’s signaling activity is the basis of ongoing study for Vande Woude and his team in the Laboratory of Molecular Oncology. They’re working to determine the feasibility of using Met expression or anti-Met antibodies as detection and prognostic tools for physicians.    

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