Pancreatic Cancer Uses Alternative Fuel to Grow in a Hostile Environment

A metabolic cross-talk pathway between cancer and noncancer cells in pancreatic tumors delivers an alternative nutrient to the cancer cells, facilitating tumor growth.

7:00 AM

Author | Nicole Fawcett

Inside a pancreatic tumor is a hostile environment. Cancer cells are choked off from the blood vessels, blocking access to oxygen and nutrients.

SEE ALSO: Starving Pancreatic Cancer by Targeting Cell Metabolism

"In principle, you would not expect cells to be able to survive under these circumstances, but in fact they thrive. They are highly adaptable and find ways to cope in this harsh environment," says Costas Lyssiotis, Ph.D., assistant professor of physiology and medicine at the University of Michigan Health System.

His team has discovered one key to how this happens. It's a metabolic cross talk in which cancer cells call out for nutrients, and nearby normal cells in the pancreas, called pancreatic stellate cells, feed the cancer. The food, in this case, is the amino acid alanine. Their study is published in Nature.

Typically, cells feed on certain types of nutrients. Lipids and carbohydrates like glucose are common examples. But when those aren't available, researchers showed, cancer finds other options.

"Alanine is an alternative fuel that the cancer co-opts. By expanding the profile of nutrients that cancer cells utilize for growth and survival, they gain a competitive advantage," Lyssiotis says.

The process at work

In both cell models and mice, the researchers showed that a process called autophagy is required for the metabolic cross talk that turns alanine into a fuel source. Autophagy is a cellular recycling process that degrades old, damaged cargo, like organelles or protein. In this metabolic pathway, the cancer cells release a signal to the pancreatic stellate cells to engage autophagy, which results in protein degradation and alanine release. The cancer cells capture this alanine and use it to grow.

SEE ALSO: Determining When Early Breast Cancer Is Aggressive — and When It's Not

In mouse models, when the researchers blocked autophagy in the stellate cells, it blocked this cross talk and slowed the growth of the tumor.

Pancreatic cancer is one of the most lethal types of cancers. It's typically aggressive and does not respond well to traditional chemotherapy and radiation treatments. It's expected to be the second-leading cause of cancer deaths by 2030. New treatments are desperately needed.

The researchers think understanding these metabolic adaptations in pancreatic tumors will lead to new types of therapies that target how cancer cells absorb and use nutrients. Unlike classical treatment strategies that target the cancer cells directly, this process attacks the support cells and opens up new ideas about combination therapies.

"With this new understanding of how and where the cancer cells are obtaining nutrients, our goal now is to design drugs that block this process and hopefully make a difference in this challenging disease," Lyssiotis says.

Additional U-M authors are Christopher J. Halbrook, Li Zhang and Daniel Kremer. Other authors are Cristovao M. Sousa, Douglas E. Biancur, Xiaoxu Wang, Mara H. Sherman, Rosa F. Hwang, Agnes K. Witkiewicz, Haoqiang Ying, John M. Asara, Ronald M. Evans, Lewis C. Cantley and Alec C. Kimmelman.


More Articles About: Lab Report Pancreatic cancer Cancer: Cancer Types
Health Lab word mark overlaying blue cells
Health Lab

This article is from the Health Lab digital publication.

Media Contact Public Relations

Department of Communication at Michigan Medicine

MichMedmedia@med.umich.edu

734-764-2220

Newsletter

Get a weekly digest of medical research and innovation, straight to your inbox.

Subscribe
Featured News & Stories Microscopic slide of purple cancer cells
Health Lab
High fat diet, unregulated athletic exercise endurance enhancers linked to risk of pancreatic cancer
A study suggests substances touted to improve athletic performance can activate a receptor that accelerates the progression of pre-cancerous lesions to pancreatic cancer in mice.
Men scientists facing each other in front of lab screen
Health Lab
Pancreatic cancer cells feed off hyaluronic acid
Often found in beauty products and wellness supplements, hyaluronic acid attracts and retains water well. It’s also a major player in the physiology of pancreatic tumors.
purple black red cell image close up
Health Lab
New Map of the Immune Landscape in Pancreatic Cancer Could Guide Future Personalized Immunotherapy Treatments
The analysis highlights the diversity of immune response in pancreatic cancer, and points toward the need for treatments tailored to individual patients.
pancreatic cancer graphic
Health Lab
Study Suggests Method to Starve Pancreatic Cancer Cells
Rather than attacking cancer cells directly, new cell-model research probes weaknesses in pancreatic cancer’s interactions with other cells to obtain nutrients needed for tumor growth.
Dr. Meredith Morgan, Dr. Kyle Cuneo, and Dr. Ted Lawrence
Health Lab
New Drug Shows Encouraging Survival Results for Pancreatic Cancer
An early clinical trial on pancreatic cancer research finds a Wee1 inhibitor, combined with radiation and gemcitabine, is safe and potentially effective in pancreatic cancer treatment.
Doctors looking at screen
Health Lab
Tumor-Associated Immune Cells Hinder Frontline Chemotherapy Drug in Pancreatic Cancer
Researchers have shown how tumor-associated macrophages release compounds that block gemcitabine in the most common type of pancreatic cancer