In the world of cells, nobody starts out as a cancer cell. Instead, a cancer cell is a normal cell that has gone bad, through a series of changes that allows it to grow and divide without stopping, and worse, to move into other regions of the body. Angelo M. De Marzo, M.D., Ph.D., the Peter Jay Sharp Foundation Scholar, describes a cancer cell as a "caricature of a normal cell."
What do stem cells have to do with this process? And why are scientists who study cancer so interested in them? There are two major types: The most controversial stem cells, embryonic stem cells, are in all of us before birth. They are the ultimate chameleons, they can become any type of cell in the body. And then there's the tissue stem cell. These aren't just in embryos, they're in all of us as adults, too, in places like our hair, skin, bone marrow, intestine, and prostate. Not as versatile as the embryonic form, they can only make a limited number of cell types. "Normally, cells can divide only a few times," explains De Marzo, "before they permanently exit from the cell cycle.
Why are stem cells so interesting
to scientists who study cancer?
They either die, or they undergo a process called "differentiation," in which they mature though a number of steps, ultimately becoming fossilized, non-dividing versions of their former selves." Stem cells, on the other hand, can divide indefinitely. In this, they are like cancer cells. But are the tissue stem cells the actual cells that go on to become cancer cells? This is a popular idea in science at the moment. Or, do other tissue cells somehow revert back to an embryonic, stem-like state?
De Marzo tends to think it's this second scenario. One of the abnormal things in a cancer cell is a structure called a nucleolus. "It's a little factory," he says, "that produces crucial components, including ribosomes; cancer cells need ribosomes to reproduce efficiently." De Marzo and colleagues recently have uncovered a potential new link between stem cells, cancer cells, and the nucleolus. It's a gene called MYC (pronounced "mick"). "MYC overproduction has been implicated in driving the formation of prostate cancer and many other cancers," says De Marzo. Recently, a study led by De Marzo's laboratory found evidence that MYC can cause prostate cells to induce a set of genes that are expressed together mostly in embryonic stem cells, and not tissue stem cells. "Thus, MYC appears capable of reactivating maturing prostate cells," says De Marzo, "acting as the ultimate fountain of youth, so that they become like embryonic stem cells, and keep on renewing themselves and dividing." The study was conducted by Cheryl Koh, a graduate student in pathobiology, in collaboration with Martin Aryee, Ph.D., Vasan Yegnasubramanian, M.D., Ph.D. and Bora Gurel M.D., at the Sidney Kimmel Comprehensive Cancer Center, and Chi Dang, M.D., Ph.D., from the Nathans Institute of Genetic Medicine at Hopkins. One of the genes induced by MYC is called fibrillarin, which concentrates in the nucleolus, and which Koh and Gurel found is overproduced in prostate cancer cells. What implications does this have? "The really exciting part," says De Marzo, is that when Koh turned down the production of MYC or fibrillarin, "the cancer cells lost their stem cell properties and could no longer proliferate. This raises the possibility that treatments that target the abnormal nucleolus may be a new avenue to pursue in the search for ways to prevent and treat prostate cancer."