Nav: Home

Gastric cancer fueled by 'crosstalk' between nerves and cancer cells

December 15, 2016

NEW YORK NY (December 15, 2016)--Gastric tumors are started by specialized cells in the stomach that signal nerves to make more acetylcholine, according to a study in mice. The multinational team of researchers who conducted the study also identified a substance called nerve growth factor that stimulates nerve development and, when blocked, inhibits stomach cancer development.

The findings were published today in Cancer Cell.

Previous studies have shown that nerves are abundant in the gastric tumor microenvironment. In an earlier paper, the researchers demonstrated that inhibiting signaling by the neurotransmitter acetylcholine, by severing the vagus nerve in the stomach or treating with Botulinum toxin, shrank or prevented the growth of gastric tumors in mouse models.

"Nerves and acetylcholine clearly play a key role in regulating the development and growth of cancer cells, particularly cancer stem cells, in the gastric tumor microenvironment," said Timothy C. Wang, MD, the Dorothy L. and Daniel H. Silberberg Professor of Medicine at Columbia University Medical Center (CUMC) and senior author of the paper. "But little is known about what is driving cancer in the earliest stage of development, before the expansion of nerves in the microenvironment. We also wanted to find out where acetylcholine is coming from before the growth of nerves."

Through a series of experiments in mouse models, the researchers determined that a neurotrophin (substance that triggers nerve growth) called nerve growth factor is highly expressed in gastric cancer cells. They also discovered that tuft cells--specialized cells found in the lining of the digestive tract that, like nerves, communicate with other cells--provide another source of acetylcholine for cancer cell growth, particularly during the formation of tumors.

"We learned that tuft cells are increased during the earliest stage of gastric tumor development, making acetylcholine and stimulating the production of nerve growth factor within the lining of the stomach," said Dr. Wang. "As nerves grow in around the tumor, tuft cells decrease."

In additional experiments, the scientists showed that overexpression of nerve growth factor in the mouse stomach drove tumorigenesis. Furthermore, administration of a nerve growth factor receptor inhibitor prevented stomach cancer in the mice.

"Our study provides some insight into the cellular crosstalk that leads to the development of stomach cancer, and points to a viable therapeutic target for this type of cancer," said Dr. Wang. "Using our findings as a paradigm, additional studies can be done to identify the specific neurotrophins and neurotransmitters that are involved in tumor development in other areas of the body."
-end-
The study is titled, "Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling." The other contributors are: Yoku Hayakawa (University of Tokyo, Tokyo, Japan), Kosuke Sakitani (University of Tokyo), Mitsuru Konishi (University of Tokyo), Samuel Asfaha (University of Western Ontario, Ontario, Canada), Ryota Niikura (University of Tokyo), Hiroyuki Tomita (Gifu University Graduate School of Medicine, Gifu, Japan), Bernhard W. Renz (Hospital of the University of Munich, Munich, Germany), Yagnesh Taylor (CUMC), Marina Macchini (CUMC). Moritz Middlehoff (CUMC), Zhengyu Jiang (CUMC), Takayuki Tenaka (CUMC), Zinaida A. Dubeykovskaya (CUMC), Woosook Kim (CUMC), Xiaowei Chen (CUMC), Aleksandra M. Urbanska (CUMC), Karan Nagar (CUMC), Christoph B. Westphalen (Klinikum der Universität München, Munich, Germany), Michael Quante (Technische Universität München, Munich, Germany), Chyuan-Sheng Lin (CUMC), Michael D. Gershon (CUMC), Akira Hara (Gifu University Graduate School of Medicine), Chun-Mei Zhao (Norwegian University of Science and Technology, Trondheim. Norway), Duan Chen (Norwegian University of Science and Technology), Daniel L. Worthley (University of Aidelaide, Australia), and Kazuhiko Koike (University of Tokyo).

The study was supported by grants from the National Institutes of Health (U54CA126513, R01CA093405, R01CA120979, and R01DK052778), the Clyde Wu Family Foundation, the Nakayama Cancer Research Institute, the Okinaka Memorial Institute for Medical Research, and the Project for Cancer Research and Therapeutic Evolution from the Japan Agency of Medical Research and Development. Y.H. and K.S. were supported by Japan Society for the Promotion of Science, and Y.H. and T.T. were supported by Uehara Memorial Foundation.

The authors declare no conflicts of interest.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. The campus that Columbia University Medical Center shares with its hospital partner, NewYork-Presbyterian, is now called the Columbia University Irving Medical Center. For more information, visit cumc.columbia.edu or columbiadoctors.org.

Columbia University Medical Center

Related Cancer Articles:

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.
Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.
Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

How to Win Friends and Influence Baboons
Baboon troops. We all know they're hierarchical. There's the big brutish alpha male who rules with a hairy iron fist, and then there's everybody else. Which is what Meg Crofoot thought too, before she used GPS collars to track the movements of a troop of baboons for a whole month. What she and her team learned from this data gave them a whole new understanding of baboon troop dynamics, and, moment to moment, who really has the power.  This episode was reported and produced by Annie McEwen. Support Radiolab by becoming a member today at Radiolab.org/donate.