Shedding Light on a Path to Halting Deadly Pancreatic Cancers

Pancreatic cancer has a dismal prognosis: only a quarter of those diagnosed survive past one year and only about six percent live beyond five years. Its strong resistance to chemotherapy makes pancreatic cancer one of the most aggressive, deadly cancers and leaves doctors with few treatment options. New ways to study pancreatic cancer are desperately needed to find novel therapies.

Today, UCSD researchers, funded in part by CIRM, report in Nature on the development of a live imaging technique that enables precise tracking of drug resistant cancer stem cells within a pancreatic tumor. Using this method, they establish that the function of a gene called Musashi (Msi) is crucial for tumor growth, making it a promising target for chemotherapy drug development.

pancreatic_cancer_imaging

Activity of stem cell gene Musashi in human pancreatic cancer. Cancer cells are shown in green, Musashi expression in red and blue includes cells within the cancer microenvironment. Image courtesy of Dawn Jaquish, UC San Diego.

The Msi protein normally plays a role in the maintenance of stem cells but it’s also known to help sustain the growth of blood cancers. The UCSD team chose to investigate the role of Msi in pancreatic cancer as they found Msi was present in every human tumor sample they tested. To track Msi in a living animal, they genetically engineered mice that would emit fluorescence in cells where the Msi gene was activated.

Cells expressing the stem cell gene Musashi (green) are shown among other tumor cells (blue) and blood vessels (pink). Musashi-expressing cells preferentially drive tumor growth, drug resistance and lethality. UCSD

Those Msi mice were then bred with another strain of mice that mimic the pancreatic cancer seen in humans. In the resulting mice, cells with a strong fluorescent signal (indicating a high level of Msi) were found as a rare, distinct population in pancreatic cancer cells. It turns out that cancer stem cells, the cells thought to be responsible for cancerous growth and treatment relapse, are also known to make up a tiny portion of a tumor. So then, do Msi-positive cancer cells have cancer stem cell-like behavior? The answer appears to be “yes”. When the team transplanted the cancer cells with high levels of Msi from one mouse into the pancreas of healthy mice, every mouse tested died from very aggressive tumor growth. On the other hand, mice transplanted with cancer cells lacking the Msi fluorescent signal showed no evidence of disease.

These very promising results, along with the new imaging toolset, not only bode well for future treatments of pancreatic cancer but also for the cancer field as a whole. In a university press release, principal investigator Tannishtha Reya detailed this point:

pancreaticTannishtha Reya

Tannishtha Reya

“Because Msi reporter [fluorescence] activity can be visualized by live imaging, these models can be used to track cancer stem cells within the tumor microenvironment, providing a real-time view of cancer growth and metastasis, and serving as a platform to test new drugs that may be better able to eradicate resistant cells.”

Let’s hope that this research path leads to the day that a pancreatic cancer diagnosis isn’t an almost certain death sentence.

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