The role of neuronal activity in the early and late stages of cancer metastasis

• Applicant: Chenchen Pan, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451894423

The majority of cancer patients die because of the wide spread metastases, and not from the primary tumor. Thus, understanding the driving mechanisms behind metastasis is critical to develop more effective cancer therapies. In recent years, more and more studies suggested a strong link between neuronal activity and cancer metastasis. However, due to the technical limitations of the standard whole-body imaging techniques, the cellular level holistic analysis of the distribution and correlation between metastases and neuronal structures at whole-body scale was not possible. To circumvent these hurdles, we developed vDISCO whole-body immunolabeling and tissue clearing protocol to visualize the neuronal structures and metastases, and integrated with DeepMACT deep learning-based algorithm to automatically detect and quantify the metastases down to single disseminated cancer cells in the entire transparent mouse bodies. We will apply these robust methodologies to study the colocalization between nerve fibers and various types of cancer metastases in xenograft and syngeneic mouse models at both early and advanced stages of tumor progression. In addition, we will apply the in vitro and in vivo assays of neuronal signaling inhibitors to systematically evaluate the efficacy of neuronal signaling based therapies against cancer metastasis. Taken together, this first thorough study of the correlation between neuronal activity and cancer metastasis could convey novel therapeutic targets to control the global metastases formation and finally benefit millions of cancer patients.

• DFG Programme: Research Grants