Okayama University Research: The Nervous System can Contribute to Breast Cancer Progression

OKAYAMA, Japan, Oct. 18, 2019 /PRNewswire/ -- In a recent study published in Nature Neuroscience, researchers at Okayama University developed a method to stimulate different types of nerves within breast tumors and found that while some nerves abetted tumor growth, some prevented it.

Autonomic nerves are messengers that carry signals from the brain to the organs in our body. In recent years, scientists have found several links between the autonomic system and cancer. Autonomic nerves are involved in the progression of prostate cancer. On the other hand, prostate and breast cancer patients can have a lower risk of death when given nerve-blocking drugs. However, the direct relationship between the autonomic system and breast cancer is still unclear. A research team led by Professor KAMIYA Atsunori at Okayama University has now examined autonomic nerves found within breast tumors and unraveled their contribution to tumor growth.

Our organs are permeated by multiple nerves. Hence, isolating and analyzing any one nerve type is tough. Additionally, targeting nerves only within the breast tumor is also difficult. To circumvent these challenges, the research team developed a virus-based tool. This consisted of an innocuous virus with the ability to genetically modify tissues to stimulate or suppress specific nerve types. In this case, the two main autonomic nerves of interest were sympathetic and parasympathetic nerves. Since the virus would have to be injected, it would only bring about these changes within the injected tissues.

The tool was first tested on breast tumors implanted into rats. Stimulating the sympathetic nerves in these rats resulted in growth of tumors. The tumors also spread to distant organs such as the lungs. Conversely, stimulation of the parasympathetic nerves resulted in reduced tumor growth. These tumors also showed a lower presence of immune checkpoint inhibitors, which are cancer-promoting proteins. The virus was then injected to inhibit the two nerve types within the tumors. Deactivating the sympathetic nerves suppressed the growth of tumors while deactivating parasympathetic nerves promoted their growth.

The team subsequently scrutinized the distribution of nerves within tumor samples of 29 breast cancer patients. The patients with a high presence of sympathetic nerves were indeed the ones with lower chances of survival, while those with a high abundance of parasympathetic nerves, had better chances of survival. The tumor samples with higher parasympathetic presence also had fewer immune checkpoint inhibitors.

This study is the first to show how stimulation of different nerves within breast tumors can determine the fate of the cancer. "Genetic sympathetic nerve denervation and parasympathetic neurostimulation of tumors may suppress breast cancer progression and are therefore a potential novel therapeutic approach for breast cancer," conclude the researchers.

Background

The autonomic nervous system: The autonomic nervous system, which comprises sympathetic and parasympathetic nerves, transmits signals from the brain to all the organs in the body. These nerves are thus vital for our organs such as the stomach, pancreas and liver to function smoothly at all times. Hyperactivity or hypoactivity of these nerves can have a significant impact on the organs they target.

Sympathetic nerves are excitatory in nature and stimulate organ function primarily under conditions of perceived threat. In contrast, the parasympathetic nerves control organ function when the body is at rest. A balance between the two is therefore very important for our organs to perform effectively under different conditions.

Reference

Atsunori Kamiya, Yohsuke Hayama, Shigeki Kato, Akihiko Shimomura, Takushi Shimomura, Katsumasa Irie, Ryosuke Kaneko, Yuchio Yanagawa, Kazuto Kobayashi, Takahiro Ochiya. Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression. Nature Neuroscience, July 2019.

DOI : https://doi.org/10.1038/s41593-019-0430-3

https://www.nature.com/articles/s41593-019-0430-3

Correspondence to

Professor KAMIYA Atunori, M.D., Ph.D.
Department of Cellular Physiology,
Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku,
Okayama 700-8558, Japan
E-mail: [email protected]  
http://okayama-u-physiol1.jp/index.html

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Okayama University is one of the largest comprehensive universities in Japan with roots going back to the Medical Training Place sponsored by the Lord of Okayama and established in 1870. Now with 1,300 faculty and 13,000 students, the University offers courses in specialties ranging from medicine and pharmacy to humanities and physical sciences. Okayama University is located in the heart of Japan approximately 3 hours west of Tokyo by Shinkansen.

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