Cells Behaving Badly: Rogue Stem Cells Set Stage for Lung Cancer, CIRM-Funded Study Finds

Occasionally, too much of a good thing can turn bad, an adage confirmed in a study published today by UCLA scientists.

Led by Dr. Brigitte Gomperts, a team of stem cell experts have honed in on how adult stem cells residing in the lung spring into action in order to repair damaged tissue. Normally, this process is vital for maintaining tissue health. But sometimes, things can go awry—thus setting the stage for cancer.

Scientists have hypothesized that some type of regulatory molecule pulled the strings—launching adult stem cells into action after injury or disease—but identifying that molecule had proven far more difficult.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

Scientists have discovered how out-of-control adult stem cells lead to pre-cancerous lesions in the lung.

In this study, published online today in the journal Stem Cell, Dr. Gomperts and her team believe they have found this molecular puppet master: a class of molecules called reactive oxygen species, or ROS.

Recently, scientists observed low levels of ROS to play a role in maintaining a variety of cellular functions. They had also noticed that while low-to-moderate ROS levels were essential, any spike in ROS appeared to have a toxic effect on the cell.

In this study, which was supported by a CIRM New Faculty Award, the UCLA team found that a ‘dynamic flux’ in ROS levels from low to moderate helped drive adult stem cells to grow and divide at regular rates and repair damaged tissue. But when ROS levels got too high, the stem cells started dividing out of control, leading to what Gomperts called “pre-cancerous lesions.”

As she explained in today’s news release:

“Low ROS is what keeps stem cells in a ready state so that your body is poised and ready to respond to injury and repair. Loss of this ROS regulation leads to pre-cancerous lesions.”

Importantly, the team noted that many environmental factors are linked to an increase in ROS levels—such as exposure to cigarette smoke, smog or pathogens. Lung cancer remains the deadliest form of cancer in the United States. Therefore, finding a way to identify the cancer in this early, pre-cancerous stage, is crucial for reducing the risk of death.

As Gomperts put it:

“Now, with this precancerous model in place, we can begin looking for what we call ‘driver mutations,’ or those specific changes that take the pre-cancerous lesion to full-blown cancer.”

Gomperts is optimistic that this ‘personalized’ approach to drug discovery will lead to more effective therapies:

“There are likely multiple ways for a patient to get a pre-cancerous lesion so the process could be different amongst different groups of people. Imagine a personalized way to identify what pathways have gone wrong in a patient, so that we could target a therapy to that individual.”

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