Two Johns Hopkins University researchers have identified a crucial change that occurs when normal cells turn into tumor cells, a change that could be a key to how cancers work, acccording to a report in a scientific journal published today.
The change is new evidence that supports the widely held belief about the nature of cancer--that cancer cells are simply normal cells with a few damaging, normally inactive genes that somehow are freed and turned on again.
"Whatever cancer is," said Andrew Feinberg, one of the researchers, "it has to do with turning on genes that should be quiet."
For example, genes for fast growth that normally are active only during the time an animal is an embryo, might create the abnormal growth that characterizes tumors if they were turned back on in adult cells.
Also, the genes that fetal cells use to invade others to force the development of the body's organs are still present throughout life, but are turned off. If those genes are turned back on, a normal cell might again invade neighboring cells, as tumor cells do.
In their work reported in the Jan. 7 issue of the journal, Nature, Feinberg and Bert Vogelstein took both normal cells and tumor cells from the colon, lungs and liver in five cancer patients.
They checked three genes in each of the cancer cells--two for blood manufacture and one that makes human growth hormone. Each of the three genes is normally turned off by being "covered up" or "methylated" with chemicals called methyl groups. This happened in the patients' normal cells the scientists studied.
But when they took tumor cells from the colon, lung and liver tumors in the patients, the same three genes were not covered in four of the five patients. The genes were "demethylated," or freed of their chemical bondage in the tumors, and thus conceivably ready to be active genes invading inappropriate cells.
The difference between the same genes in normal and tumor cells suggested at least one important way cancer can occur--demethylating genes such as those for growth or, for in the case of rapid embryo growth, for invasion of other cells.
Feinberg and Vogelstein said the general theory is especially attractive because it may explain several unusual features of cancer.
Cancer cells can move from one body organ and invade another. This is bizarre behavior for normal, adult cells, but it is common in the cells of embryos.
So, if the genes that cause migration in embryos were turned on again in adults, the transport of cancer cells could be explained.
It would also help explain why tumor cells produce unusual chemicals and hormones--because the genes for making these may have been freed unexpectedly for manufacture by demethylation.
But the critical question about the work reported today, and about the general theory of cancer it supports, the scientists say, is whether demethylation is a direct cause of cancer or only a side effect when cells become cancerous.
"Further research will be required to understand fully the significance of these changes in DNA methylation," Vogelstein said. "One can be certain, however, that the elucidation of these . . . changes will be crucial in understanding cancer and eventually developing new methods of treating or preventing it."