Robert Weinberg, MIT professor of biology and Whitehead Institute for Biomedical Research member, has created cancer stem cells in a Petri dish by isolating and transforming a particular population of cells from human breast tissue. After being injected with just 100 of these transformed cells, mice developed tumors that metastasized (spread to distant tissues).
“The operational definition of a cancer stem cell is the ability to initiate a tumor, so these are cancer stem cells,” declares Weinberg, who is also an MIT professor of biology.
Engineering these potent cells was not the original intent, says pathologist Tan Ince. As a post-doctoral researcher in the Weinberg lab and gynecologic pathologist at Brigham and Women’s Hospital, he was simply trying to create breast cancer models that look like real human tumors under the microscope and behave like those seen in many patients.
In more than 90 percent of human breast tumors, cancer cells resemble those lining our body’s cavities. A trained pathologist can spot the similarities under a microscope. But the cancer cells previously engineered from normal breast cells for laboratory studies looked different. Ince suspected that researchers were transforming the wrong type of cells.
Now an independent investigator at Brigham and Women’s Hospital and an instructor at Harvard Medical School, Ince developed a recipe for a new chemically defined culture medium and managed to grow a different type of human breast cell that ordinarily dies in culture. He transformed it into a cancer cell by inserting specific genes through a standard procedure.
The engineered cells proved to be extremely powerful. When Ince injected more than 100,000 of them into a mouse with a compromised immune system, it quickly developed massive, deadly tumors. In initial experiments, a few tissue slices revealed a primary tumor structure that resembled that of cancer patients with metastases.
That prompted Ince to wonder whether the cancer cells he created would metastasize if the mouse lived longer. He repeated the experiment in other mice, reducing the number of cells in the injection to as few as 100 in hopes of slowing tumor growth. The cancer cells continued to seed tumors and those tumors metastasized. In sharp contrast, scientists must inject about 1 million cells to get a tumor when working with the cancer cell lines routinely used in the laboratory.
“In the process of making a model that reflects a tumor type common in patients, I created tumor-initiating cells,” Ince explains. “That was a complete surprise.”
“This work could provide a boon to researchers who study these elusive cancer stem cells by offering a bountiful source of them,” maintains Weinberg. “Labs can easily grow the newly created cells for use in experiments.”
Source: Whitehead Institute for Biomedical Research
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