By Sue Rochman
Growth Factors: Jekyll and Hyde
These protein bosses can make cells go haywire, but they've also provided targets for new cancer patients
By Sue Rochman
The human body is a cellular factory with somewhere between 10 trillion and 100 trillion cell employees. Day in and day out, these cells participate in a complex manufacturing process that produces more than one trillion new cells every day. It's a complicated business that requires many rules and regulations to stay on track. To avoid anarchy, proteins called growth factors function as the supervisors of cell growth and tell cells when to divide. Factory rules govern exactly how a growth factor speaks to a cell: It must communicate through a special receptor—another protein—that sits on the cell's surface. Adding to the bureaucracy, a growth factor is not permitted to communicate with just any receptor. It can converse only with a receptor that speaks its specific language.
"Think of growth factors and growth factor receptors as a unit," explains pathologist Michael Ittmann of the Baylor College of Medicine in Houston. "Growth factors are [proteins that] are secreted by the cell, and receptors are the proteins on the surface of the cell that bind to those growth factors."
Growth factors (purple and yellow) bind to receptors (blue and green) that protrude from a cell's surface. A cross-section view shows how the opposite end of each receptor reaches the inside of the cell (deep red area). [Art: Nicolle Rager Fuller]
The first growth factor to be identified was a nerve growth factor discovered in the 1950s by the developmental biologist Rita Levi-Montalcini. In 1986, she shared a Nobel Prize with the American biochemist Stanley Cohen who, in the early 1960s, discovered a second growth factor, called the epidermal growth factor. Their work, which illuminated how the growth and differentiation of a normal cell is stimulated and regulated, also helped explain how cancer cells operate.
Over the past 50 years, researchers have discovered many more growth factors, some related to cancer. How many growth factors are there? "Too many to count," says oncologist Amit Verma of the Albert Einstein College of Medicine in New York City.
"But what's important is that particular growth factors act only on specific cells."
To send its message, a growth factor seeks out its partner receptor on a cell's surface. Growth factors and receptors are supposed to communicate only when the body needs more cells. But as in any factory, sometimes errors occur. In some instances a cell begins to produce too much growth factor, which can result in receptors transmitting too many growth messages to the cell. In other cases, genetic mistakes cause extra receptors to appear on a cell's surface, creating additional opportunities for the growth factors to communicate with the cell. This unsanctioned, unruly communication can lead to one of the hallmarks of cancer: uncontrolled cell growth.
By identifying this communication process, scientists exposed some of the inner workings of the cellular factory, enabling them to pursue the development of special agents—drugs—that could intervene and help the body regain control of its errant work force. As this research got under way, researchers realized that the best approach was to block the receptor, not the growth factor. If you block production of the growth factor, the body may respond by "starting to churn out more and more of it," says Verma, defeating the drug's purpose. "It's easier to block the receptor, because there are only a certain number of receptors a cell can make."