Cancer researchers have purposely engineered cancer cells in humans for the first time, bringing researchers one step closer to understanding how cancer grows.
Researchers at the Whitehead Institute for Biomedical Research genetically engineered the first human cancer cells by tricking the cells into producing an enzyme called telomerase, and creating a cocktail with two cancer-causing genes, or oncogenes.
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"Normal human cells don't have active telomerase, but they have the blueprint to make it," said William Hahn, a postdoctoral fellow in oncology at Whitehead and an oncologist at the Dana-Farber Cancer Institute. "In cancer, the cells take the blueprints and turn them on to make the telomerase enzyme."
The researchers took their cue from previous research done on mice. Fifteen years ago, scientists led by Jonathan Weitzman, also the lead researcher on the present study, found it a simple task to put oncogenes into mouse cells and generate cancer. However, it never worked in humans until now.
"In mouse cells, if you take two oncogenes, you can turn normal cells into cancer," Hahn said. "Normal human cells don't have any telomerase, but cancer cells do."
Mice have telomerase active in their cells all the time, and it turns out that's what makes it easy to induce cancer in the rodents.
"We thought maybe that was the difference, so we put telomerase and the two oncogenes into human cells and we got cancer cells," Hahn said. "The take-home message was that human cells have an additional barrier in preventing cancer."
The researchers used two types of oncogenes. One switches on so some cells are stuck in a constant grow state. The other disables a signal telling certain cells to stop growing.
Telomerase affects the control system that dictates how many copies a cell can make of itself. Normally, there is a limit to how many copies it can make, but the telomerase turns that system off.
"The idea of telomerase has been around for a while now, so the success here is finding exactly the right cocktail of genes that you have to add to a cell to convert it from a normal cell to a tumor cell," said Christopher Widnell, scientifc program director for molecular cell biology at the American Cancer Society.
One important conclusion the researcher reached was that there is a finite number of molecular pathways that produce the abnormal traits that make a tumor cell.
"Someday, we'd like to be able to say that the way you turn a normal cell into a cancer cell depends on a certain number of changes and we know what all these changes are," Hahn said.
"If you know all the changes to make the cancer cell, you know all of the important changes you need to make a drug against them," he added. "It will take a long time to get there, but this is a significant step in looking at cancer in a slightly different way."
Since the cancer cells generated were not metastatic (the type of cancer cells that spread to other organs), the Whitehead researcher has more studies planned to make them metastatic to learn about that process.
"That's a very complex thing to study in the lab. And it's been pretty hard to do up until now," Hahn said. "Since [these cells] don't metastatize, we can use them as a tool to see how they will."
The researchers now know that they can turn on the telomerase in humans, but they still don't know why it happens on its own. That's another area for future research.
"We tricked the cells into making the telomerase, but we still don't know how they turn it on [on their own]," Hahn said. "We're actively looking at it, but it looks like it's going to be pretty complicated."
Widnell was more optimisitc.
"So much significant progress has been made in so many areas in the last decade, and the number of studies in this area and the quality of the investigators studying these problems both suggest that we might get answers sooner than we think," Widnell said. "It could turn out to be much more soluble than people fear."
