Uncovering the “symbiotic dance” of cancer cells and neurons

　　【Today’s Viewpoint】

　　◎Our reporter Liu Xia

　　Scientists from Stanford University in the United States published a paper in Nature magazine, confirming for the first time that malignant brain cancer is closely related to the brain's neural connections. They found that gliomas "communicate" with healthy neurons, forming synapses that hijack electrical signals from healthy neurons to promote their own growth.

　　According to a recent report on the British "Nature" website, many scientists are conducting a new round of research, trying to understand the inextricable connections between cancer and neurons, and hope to develop new methods to treat cancer on this basis.

Neurons "connect" with cancer cells

　　Nearly 200 years ago, scientists first discovered the connection between cancer cells and neurons. In the mid-19th century, French anatomist Jean Cluvier described a case in which breast cancer had invaded the cranial nerves responsible for facial movement and sensation. This is the first time scientists have described cancer attacking nerves.

　　In the late 1990s, Gustavo Ayala, a urological pathologist at the University of Texas, began to study more deeply the interaction between neurons and cancer cells. He placed mouse nerves in a petri dish containing human prostate cancer cells. After about 24 hours, he saw the nerves starting to grow small branches called axons, which stretched toward the cancer cells. Once the two come into contact, the cancer cells spread along the nerve until they reach neuronal cells.

　　Ayala said nerves are not just bystanders; they actively seek connections to cancer. In 2008, Ayala reported another phenomenon: prostate tumor samples contained more nerve fibers than healthy prostate samples.

　　Then, in a groundbreaking paper published in 2013, Claire Manon, a cancer expert at the French National Institute of Health and Medical Research, and colleagues documented the growth of nerve fibers within prostate tumors in mice. The results show that high-density nerve growth in and around tumors can help prostate cancer grow and spread. Cutting off the connection with the nervous system prevents the cancer from spreading.

　　A growing body of research shows that the same happens in cancers such as stomach, pancreatic and skin cancers.

Cancer cells transform neurons

　　Research in subsequent years showed that cells within tumors can transform into neurons, or at least acquire characteristics similar to those of neurons. In 2019, Manon's team reported that they saw neural progenitor cells traveling through the bloodstream to prostate tumors in mice, where they settled and developed into neurons.

　　The next year, neuroscientist Moran Amit and others at the University of Texas MD Anderson Cancer Center discovered that cancer can force neurons to change their identity. Studies of oral cancer in mice have shown that sensory neurons that carry sensations to the brain exhibit characteristics of sympathetic neurons. This shift may help tumor growth, Amit said, because sympathetic nerves have been shown to be beneficial in some cancers.

Nerves affect different cancers differently

　　Different types of nerves have very different effects on different tumors.

　　In the case of pancreatic tumors, sympathetic nerves are involved in malignant feed-forward loops that contribute to cancer growth. They release signals that instruct cancer cells to secrete nerve growth factors, which attract more nerve fibers. The parasympathetic nerves, which are responsible for the "rest and digest" response, send out chemical messages that hinder the progression of cancer.

　　The opposite is true in gastric cancer, where parasympathetic signaling drives tumor growth.

　　In prostate cancer, both nerves contribute to tumor growth. In the early stages of prostate cancer development, sympathetic nerves help; parasympathetic nerves promote the later spread of cancer.

　　The researchers note that each cancer interacts with the nervous system slightly differently. Therefore, when developing anti-cancer programs, it is important to target different cancer types and understand how cancers connect to or use the nervous system.

　　Neurons also suppress the immune system, making it less effective at fighting tumors. A 2022 study found that calcitonin gene-related peptide, released by sensory nerves, can inhibit the activity of certain immune cells, making them ineffective in fighting cancer.

　　Jami Salomon, a cancer neuroscientist at the University of Pittsburgh, points out that neurons not only provide a pathway for cancer to spread, but also appear to provide a safe haven for cancer. Tumor cells can "tuck themselves into nerves," where they are protected because it is difficult for drugs to enter nerve tissue. (Science and Technology Daily)