The role of neuronal activity in the early and late stages of cancer metastasis
Experimental Models for the Understanding of Nervous System Diseases
Final Report Abstract
Cancer metastases related diseases are the leading cause of cancer deaths. Therefore, profound investigations of the mechanisms driving metastases progression are critical for developing effective anti-cancer therapies. There is a growing number of evidences indicating that the nervous system plays an important role in tumor growth. However, due to the technical limitations of in-depth microscopy of internal organs, the interactions between distal cancer metastases outside the brain and the local neuronal network in major organs such as in liver and lungs remain largely under discovered. Applying advanced whole-body tissue clearing technique vDISCO, we visualized the global breast cancer metastases and the entire periphery nervous system in the same mouse samples with subcellular-level resolution. The colocalization of nerve fibers and cancer metastases was evident in most internal organs including lungs, liver and pancreas. Further statistic studies are needed to analyze the correlation between innervation and metastases growth. We also conducted pharmacological and surgical denervation of internal organs in a spontaneous breast cancer metastasis model. The anti-metastatic therapeutic effects of organ denervation and neuronal singling inhibitors will be investigated in the future.
Publications
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Insights and opportunities at the crossroads of cancer and neuroscience. Nature Cell Biology, 24(10), 1454-1460.
Pan, Chenchen & Winkler, Frank
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A Cellular Ground Truth to Develop MRI Signatures in Glioma Models by Correlative Light Sheet Microscopy and Atlas-Based Coregistration. The Journal of Neuroscience, 43(30), 5574-5587.
Schregel, Katharina; Heinz, Lennart; Hunger, Jessica; Pan, Chenchen; Bode, Julia; Fischer, Manuel; Sturm, Volker; Venkataramani, Varun; Karimian-Jazi, Kianush; Agardy, Dennis A.; Streibel, Yannik; Zerelles, Roland; Wick, Wolfgang; Heiland, Sabine; Bunse, Theresa; Tews, Björn; Platten, Michael; Winkler, Frank; Bendszus, Martin & Breckwoldt, Michael O.
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Mis-localization of endogenous TDP-43 leads to ALS-like early-stage metabolic dysfunction and progressive motor deficits. Molecular Neurodegeneration, 19(1).
Hu, Yiying; Hruscha, Alexander; Pan, Chenchen; Schifferer, Martina; Schmidt, Michael K.; Nuscher, Brigitte; Giera, Martin; Kostidis, Sarantos; Burhan, Özge; van Bebber, Frauke; Edbauer, Dieter; Arzberger, Thomas; Haass, Christian & Schmid, Bettina
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Tumor biomechanics as a novel imaging biomarker to assess response to immunotherapy in a murine glioma model. Scientific Reports, 14(1).
Streibel, Yannik; Breckwoldt, Michael O.; Hunger, Jessica; Pan, Chenchen; Fischer, Manuel; Turco, Verena; Boztepe, Berin; Fels-Palesandro, Hannah; Scheck, Jonas G.; Sturm, Volker; Karimian-Jazi, Kianush; Agardy, Dennis A.; Annio, Giacomo; Mustapha, Rami; Soni, Shreya S.; Alasa, Abdulrahman; Weidenfeld, Ina; Rodell, Christopher B.; Wick, Wolfgang ... & Schregel, Katharina
