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Ariana Sattler, Ph.D., right, and Ece Eksi, Ph.D., are co-authors on a new study that found that certain nerves may support pancreatic cancer growth.
Photo Credit: OHSU/Christine Torres Hicks
Scientific Frontline: Extended "At a Glance" Summary: The Role of Sympathetic Nerves in Pancreatic Cancer
The Core Concept: Sympathetic nerves, which regulate the body's "fight or flight" stress response, can infiltrate pancreatic tumors and actively facilitate their growth by communicating with cancer cells and surrounding support cells.
Key Distinction/Mechanism: Traditional oncology has heavily focused on intra-tumor components like immune cells, blood vessels, and fibroblasts while largely overlooking the nervous system, as the main bodies of nerve cells reside outside the tumor. This new paradigm demonstrates that nerves structurally infiltrate the tumor microenvironment and chemically alter the behavior of cancer cells and cancer-associated fibroblasts to promote malignancy.
Major Frameworks/Components:
- Tumor Microenvironment Integration: Sympathetic nerves act as an external support system, directly embedding into and altering the pancreatic tumor ecosystem.
- Prognostic Genetic Markers: The presence of sympathetic-associated genes correlates with poor survival rates in human patients with pancreatic cancer.
- Sex-Specific Phenotypes: Experimental removal of sympathetic nerves in mouse models resulted in reduced tumor size exclusively in female mice, suggesting that sex hormones heavily influence nerve-tumor communication.
Branch of Science: Cancer Neuroscience, Oncology, and Biomedical Sciences.
Future Application: The findings offer a foundation for repurposing existing drugs, such as beta-blockers, to dampen stress signals and potentially starve tumors of neurological support. Additionally, it introduces the possibility of utilizing targeted nerve-stimulation devices as a novel intervention for cancer therapy.
Why It Matters: Pancreatic cancer is a highly fatal disease with limited treatment options. Proving that tumors do not grow in isolation—but instead hijack body-wide monitoring networks like the nervous system—exposes an entirely new physiological vulnerability that can be targeted for future cancer prevention and treatment.
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| Ariana Sattler, Ph.D., is first author on a new study that found that certain nerves may support pancreatic cancer growth. Photo Credit: OHSU/Christine Torres Hicks |
Oregon Health & Science University researchers have found that certain nerves that play an integral role in the body’s “fight or flight” stress response can support pancreatic tumor growth.
These nerves, called sympathetic nerves, grow directly into pancreatic tumors and communicate with cancer cells and nearby support cells known as cancer-associated fibroblasts. This communication can change the tumor’s behavior in ways that help pancreatic cancer grow.
“We were interested in gaining new insights into how sympathetic nerves interact with all of the other cells within that pancreatic cancer ecosystem, and how these interactions influence pancreatic cancer,” said the study’s first author, Ariana Sattler, Ph.D., who completed the work as a doctoral candidate in the OHSU Graduate Program in Biomedical Sciences.
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| Ariana Sattler, Ph.D. Photo Credit: OHSU |
Scientists have long studied components of the tumor ecosystem such as the fibroblasts, immune and blood vessel cells but often overlooked nerves, she said. One central reason is that the main bodies of nerve cells sit outside tumors, making them harder to detect with traditional sequencing tools.
To study the role of nerves in cancer, the team drew from prior cancer and neuroscience research to develop new marker panels and create a model to selectively remove sympathetic nerves from the mouse pancreas.
Their study results showed that sympathetic-associated genes are associated with poor survival in patients with pancreatic cancer, and removal of pancreatic nerves resulted in smaller tumors — but only in female mice. That result suggest that sympathetic nerves are an important player in pancreatic cancer, and that sex hormones may contribute to how nerves and tumors communicate.
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| Ece Eksi, Ph.D. Photo Credit: OHSU |
“The sex-specific tumor phenotype that we observed was very unexpected,” said Ece Eksi, Ph.D., assistant professor in the OHSU Knight Cancer Institute’s Cancer Early Detection Advanced Research Center and the study’s senior author.
Eksi’s lab is now continuing several projects to explore further differences in the tumor microenvironment in the absence of sympathetic nerves and how sex hormones may influence this nerve-cancer connection.
Eksi said the nervous system acts as a kind of body-wide monitoring and feedback network, constantly sensing what is happening in all organs. Because the pancreas is a gland that regularly responds to nerve signals and hormones, it may be especially sensitive to sympathetic inputs in the context of cancer.
The findings are still early, but the researchers say the work could be built upon to someday inform new treatments. Some scientists in the cancer-neuroscience space are already testing whether preexisting drugs for other uses, such as beta blockers which are typically used to manage cardiovascular conditions and dampen stress signals, might help hamper certain cancers. Recent emergence in devices that stimulate major nerves, currently used for other diseases, could one day be explored in cancer.
For now, Sattler said the study highlights a growing field known as cancer neuroscience — and a simple idea: tumors do not grow alone. They interact and are supported by several body systems surrounding them, including the nervous system. Understanding those connections could open new paths to understanding this fatal disease that needs more treatment and prevention options.
Additional information: All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.
Funding: This study was supported by the National Cancer Institute, of the National Institutes of Health, under Award numbers R01CA257452, R01CA250917; the Memorial Sloan Kettering Cancer Center under Award number P30 CA008748; as well as by funding from the Cancer Early Detection Advanced Research Center (CEDAR Project ID# Faculty Startup 2023-1768, CEDAR Project ID# Exploratory Grant 2025-2044 & 2023-1840) and the Knight Cancer Institute’s Scientific Operations Collaborative Grant.
Published in journal: JCI Insight
Authors: Ariana L. Sattler, Parham Diba, Kevin Hawthorne, Carl Pelz, Joe Grieco, Tetiana Korzun, Bryan Chong, M.J. Kuykendall, Rosalie C. Sears, Daniel L. Marks, Mara H. Sherman, Teresa A Zimmers, and S. Ece Eksi
Source/Credit: Oregon Health & Science University | Angela Yeager
Reference Number: ongy030326_02
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