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.
The study, which appears in Cancer Cell on August 13, also offers clues about the trajectory of cancer cells. A normal cell is thought to evolve progressively toward a malignant state through a series of genetic mutations. The early alterations confer uncontrolled growth, while later alterations enable the cell to migrate and invade other tissues. Over the past decades, considerable effort has gone into discovering these tumor-initiating and metastasis-initiating genetic alterations.
The new study suggests, however, that some normal cells are more prone to become tumor-initiating cells and have a higher metastatic potential when they become cancer cells than other normal cells. The culture medium Ince created favors the growth of the human b
Contact: Alyssa Kneller
Whitehead Institute for Biomedical Research