Pseudo-synaptic activation of NMDAR signal promotes brain metastasis in breast cancer

Breast cancer brain metastasis (
breast-to-brain metastasis, B2BM) has a very poor prognosis, and it is not clear why breast cancer prefers the mechanism of brain metastasisQiqun Zeng,of theInstitute ofCancer Experiments at the Federal Institute of Technology in Lausanne, Switzerland, published a paper online in nature in2019 to reveal the pathways of brain metastasis in breast cancer, starting with the activation of breast cancer metastases forneuronal glutamate receptor (
NMDAR) to activate breast cancer metastases and pre-synaptic neurons- post-synaptic neurons-star glioblastic cells to form a "triple pseudo-synaptic synaptic synaptic" to provide a "triple pseudo-synaptic growth" to provide a source of central altrucfindingsfindings,B2BM cells play a key role in metastatic tumor cultivation and are associated with poor prognosis through the neural signaling pathways activated by the glutamate receptor (NMDAR)There is not enough amount of glutamate secreted by human and mouse B2BM tumor cells to activate the NMDAR signal by forming a "triple pseudossy synapses" between tumor cells and nerve cellsfindings
the results show that the interaction between breast cancer metastasized cells and neuronal cells activates gluN2B-NMDAR signal axis inducedby glutamate in the microenvironment of the brainPrevious studies have shown that breast cancer metastasized cells can be coupled with astral glial cells through a gap connection, reprogramming them to create a favorable tumor microenvironment Therefore, breast cancer metastasis cells interact functionally with neurons and astrocytes, which promotes the metastasis and growth of breast cancer cells the ability of breast cancer brain metastasis also depends on other factors, including the ability to cross the blood-brain barrier and suppress tissue barriers Due to the high expression of nmDAR in all breast cancer subtypes
and the NMDAR signal promotes the growth of breast cancer cells, affecting clinical prognosis and may also promote the progression of breast tumors To assess this possibility, the researchers designed to use specific phosphorylation antibodies to immunize breast cancer through tissue chips to diagnose functional NMDAR signal levels breast cancer brain metastasis on The dependence of gluN2B-NMDAR signals provides a potential route for treatment However, tumor cells with brain metastases in breast cancer have an interaction with neurons, directly inhibiting the NMDAR in brain metastatic tumors that may cause neurotoxicity Future studies need to identify the effect molecules downstream of the GluN2B-NMDAR signal, which inhibit the growth of brain metastatic tumors and protect the function of neurons The authors point out that the results of the above study reveal a new mechanism, namely, gluN2B-mediated NMDAR signal synapses activatebreast cancer metastasis cells through "triple pseudosysysyness", which promotes the secondary secretion of glutamate receptors, reflecting the correlation between "seeds and soil" in the theory of organ selective metastasis.