New technique creates cancer stem cells

Apr 09, 2008

With a bit of genetic trickery, researchers at the Stanford University School of Medicine have turned normal skin cells into cancer stem cells, a step that will make these naturally rare cells easier to study.

Cancer stem cells are thought to be the ones that drive a cancer, and are therefore the targets of any cancer therapy that must kill them in order to be effective. Understanding these cells has been a challenge, however, because they are rare, difficult to isolate and don't grow well in the lab.

Howard Chang, MD, PhD, assistant professor of dermatology and senior author of the work, said being able to generate cancer stem cells from normal cells will help move that research forward. "The upshot is that there may be a way to directly create cancer stem cells in the lab so you don't always have to purify these rare cells from patients in order to study them directly," he said. The work will be published in the April 10 issue of Cell Stem Cell.

The study also demonstrated that cancer stem cells are much more similar to the stem cells found in embryos, which can develop to form all tissue types, than they are to the more-restricted adult stem cells. This finding has important implications for understanding how cells go awry when they become cancerous.

Cancer stem cells were first discovered in 1994 by researchers at the University of Toronto. In 2003, Michael Clarke, PhD, who was then at the University of Michigan, discovered cancer stem cells in the first solid tumor, breast cancer in this case, showing that the concept of cancer stem cells wasn't restricted to blood cancers. Clarke has since moved to Stanford, where he is the Karel H. and Avice N. Beekhuis Professor in Cancer Biology, and Stanford has become a leader in cancer stem cell research, with teams finding cancer stem cells in head and neck cancer, colorectal cancer and additional blood cancers. Laboratory researchers at the medical school are also beginning to work with clinical groups to apply cancer stem cell findings to patient care.

One question among cancer stem cell researchers has been how those cells originate. "By the time a patient comes to a hospital, they already have a cancer, so that process has already happened," Chang said. Generating cancer stem cells in the lab gives scientists insight into how the transformation happens and could lead to new ways of either stopping the transformation early on or detecting and destroying those cells once they form.

Chang and first author David Wong, MD, PhD, postdoctoral scholar, began to answer the question of how cancer stem cells originate by comparing genetic activity in embryonic stem cells with the activity in normal adult stem cells. They found a large group of genes that were active only in embryonic cells. They then looked at which genes were active in cancer stem cells and found that the pattern resembled that of embryonic stem cells.

The finding was a surprise, given that once embryonic stem cells become committed to forming adult cells, such as skin, brain or blood, they were thought to forever deactivate those embryonic genes. Instead, Chang said this work suggests that when those adult cells become cancerous, they turn those embryonic genes back on.

The group also noticed that the genes active in both embryonic and cancer stem cells are controlled by a few biological master regulators. One of those genes, called Myc, has also been shown recently to help convert normal skin cells into embryonic-like cells.

By activating two genes in addition to Myc in normal skin cells, those cells were transformed into what appeared to be cancer stem cells. When transplanted into laboratory mice, the cells formed tumors, one hallmark of a true cancer stem cell.

From here, Chang and Wong hope to learn more about how these genes activate a cancerous state. "Our particular interest is in using this approach to find the mechanism that turns a normal cell into a cancer stem cell," said Chang, who is also the Kenneth G. and Elaine A. Langone Scholar of the Damon Runyon Cancer Research Foundation.

Source: Stanford University

Explore further: Researchers design tailored tissue adhesives

add to favorites email to friend print save as pdf

Related Stories

Twist1: Complex regulator of cell shape and function

Jan 20, 2015

Transcription factor Twist1 is involved in many processes where cells change shape or function. Thereby, Twist1 is crucial for embryonic development, but has also been implicated in cancer progression. However, the precise ...

Using viruses to find the cellular Achilles heel

Jan 22, 2015

Back-to-back studies from researchers at the Gladstone Institutes have exposed new battle tactics employed by two deadly viruses: hepatitis C (HCV) and the Kaposi's sarcoma-associated herpesvirus (KSHV). Published in the ...

Recommended for you

Researchers design tailored tissue adhesives

8 minutes ago

After undergoing surgery to remove diseased sections of the colon, up to 30 percent of patients experience leakage from their sutures, which can cause life-threatening complications.

New cells may help treat diabetes

14 hours ago

Starting from human skin cells, researchers at the University of Iowa have created human insulin-producing cells that respond to glucose and correct blood-sugar levels in diabetic mice. The findings may represent ...

Using stem cells to grow new hair

Jan 27, 2015

In a new study from Sanford-Burnham Medical Research Institute (Sanford-Burnham), researchers have used human pluripotent stem cells to generate new hair. The study represents the first step toward the development ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.