Nature: revealing the new mechanism of breast cancer metastasis to brain

September 24, 2019 / Biovalley BIOON / - -- in 2018, breast cancer is the most common cancer among women in the world, accounting for about a quarter of all cancers reported When breast cancer metastases, the brain is a common destination The high incidence of breast to brain metastases (b2bm) has led scientists to speculate that there is an internal reason for breast cancer cells to migrate to the brain and plant tumors Clarifying this internal reason may provide us with the means to minimize or even completely prevent b2bm In a new study, researchers from the Swiss Institute of experimental cancer (isrec), affiliated to the Federal Institute of Technology (EPFL) in Lausanne, Switzerland, found that b2bm involves the N-methyl-D-aspartate receptor (NMDAR), which is present on the cell membrane of neurons and is involved in the transmission of nerve impulses NMDAR is activated by glutamate released from presynaptic neurons during synaptic transmission of this nerve impulse The related research results were published online in the nature Journal on September 18, 2019, and the title of the paper is "synthetic proximity enables NMDAR signaling to promote brain metastasis" The picture is from W Jiang and Q Zeng (EPFL) In the past, isrec researchers have found that glutamate activated NMDAR signal contributes to the invasive growth of neuroendocrine tumors and ductal pancreatic tumors, and this selective neuronal signal pathway is usually related to the poor prognosis of various cancer types So when these researchers started looking for the culprits for b2bm, NMDAR was at the top of the list This new study has yielded results: the researchers cultured b2bm cells in the laboratory to study their relationship with NMDAR As expected, with the help of neuron signaling pathways selected by these cells, NMDAR transmits its role to neurons This seems to indicate that the key to b2bm is to turn on NMDAR Although some cancer cells secrete enough glutamate from me to activate NMDAR, this new study found that it is not enough in breast cancer cells So, how do they activate NMDAR receptors? In a breakthrough finding, the researchers found that breast cancer cells form "pseudo tripartite synapses" with neurons that normally secrete glutamate as a neurotransmitter, because they are similar to the tripartite synapses formed between two neurons and surrounding non neuronal supporting cells, such as astrocytes Once these pseudo tripartite synapses are formed, these neurons will provide enough glutamate for breast cancer cells, which can activate NMDAR receptor, thus providing what these researchers call "the potential theoretical basis for brain metastasis" Douglas Hanahan, co-author of the paper and member of Swiss Institute of experimental cancer research, said, "this remarkable mechanism of promoting the growth of brain metastatic tumors has increased our knowledge base about brain metastasis characteristics, and we hope that it can be used for prevention and treatment The challenge lies in the potential proximity of cancer cells to normal neuronal synapses, and NMDAR signals are crucial to normal neuronal synapses Therefore, in future research, we and others will need to find specific weaknesses in glutamate triggered metastatic breast cancer cells, which can block brain metastasis and protect nearby normal neurons from damage by targeting these weaknesses therapeutically " (bio Com) reference: 1 Qiqun Zeng et al Synthetic solution enablers NMDAR signaling to promote brain metastasis Nature, 2019, DOI: 10.1038/s41586-019-1576-6 2 The path of breast to brain cancer metastasis https://mediaexpress.com/news/2019-09-path-breast-to-brain-cancer-metastasis.html