Carcinoma cells misuse the host tissue damage response to invade the brain

作者: Han‐Ning Chuang , Denise van Rossum , Dirk Sieger , Laila Siam , Florian Klemm

DOI: 10.1002/GLIA.22518

关键词: ZebrafishPathologyWound healingWnt signaling pathwayCancer researchChemokine receptorInnate immune systemMicrogliaCarcinomaNeuroinflammationBiology

摘要: The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with host tissue. comes a substantial destruction surrounding This leads to activation damage responses resident innate immune protect, repair, and organize wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, CNS, assist cell invasion. Here we report this fatal side effect physiological response In slice coculture model, contact both benign malignant epithelial induced microglia astrocytes comparable seen at interface human cerebral metastases. While glial intended protect intrusion inducing apoptosis, it proved ineffective against various types. They did not undergo apoptosis actually exploited local tissue reaction invade instead. Gene expression functional analyses revealed C-X-C chemokine receptor type 4 (CXCR4) WNT signaling were involved process. Furthermore, CXCR4-regulated recruited sites injury zebrafish model CXCR4 was expressed stroke patients, suggesting conserved role types injuries. Together, our findings point detrimental misuse program resistant glia-induced apoptosis.

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