Center for Molecular Medicine Cologne

Bergami, Matteo | Motori, Elisa - A 02

Role of synaptic hijacking in SCLC brain metastatic growth

Introduction

The finding that intractable, malignant brain tumors (i.e., glioma and glioblastoma) can hijack the local synaptic environment to sustain their own growth and invasiveness has recently sparked much attention.

These findings uncovered a previously unknown vulnerability in intractable brain tumors, where synaptic terminals are most abundant, yet the key question arises whether other types of malignant tumors outside the brain may also utilize similar mechanisms to maintain proliferation in situ or even to disseminate into brain tissue.

Building on preliminary data, we focus here on small lung cancer cells (SCLC) to investigate their capability to receive synaptic inputs by neurons and explore the possibility that this process may be relevant for SCLC brain metastasis formation and growth – a hallmark of poor survival in patients.

Clinical Relevance

SCLC is a highly metastatic neuroendocrine carcinoma with poor response to chemotherapy or radiation. SCLC dissemination to the brain is a major cause of mortality in patients, underscoring the need to identify new molecular targets for effective treatments.

The planned experiments are meant to unambiguously identify the relevance of synaptic hijacking for SCLC metastatic growth and lay the ground for the translational applicability of our findings for new effective therapies.

Approach

By employing state-of-the-art synaptic tracing, chemogenetics and imaging approaches, we will investigate to which extent the growing ability of SCLC cells may rely upon synaptic hijacking.

By these experiments we hope to acquire key insights into the mechanisms promoting SCLC brain metastatic growth.

Specific approaches:

  • Establishment of neuron-cancer cell co-cultures to investigate changes in proliferation and neurotoxicity
  • Trans-synaptic tracing approach to map the potential connectome of cancer cells
  • Viral-based approaches to manipulate gene expression in cancer cells and neurons
  • Göbel J, Engelhardt E, Pelzer P, Sakthivelu V, Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Giavalisco P, Ghanem A, Conzelmann KK, Motori E*, and Bergami M*. Mitochondria-Endoplasmic Reticulum Contacts in Reactive Astrocytes Promote Vascular Remodeling. Cell Metab (2020); 31:791-808 e8. *equal contribution.
  • Bergami M, and Motori E. Reweaving the Fabric of Mitochondrial Contact Sites in Astrocytes. Front Cell Dev Biol(2020); 8:592651.
  • Göbel J, Pelzer P, Engelhardt E, Sakthivelu V, Jahn HM, Jevtic M, Folz-Donahue K, Kukat C, Schauss A, Frese CK, Ghanem A, Conzelmann KK, Motori E, Bergami M. Mitochondrial fusion in reactive astrocytes coordinates local metabolic domains to promote vascular repair. BioRxiv (2019); doi: https://doi.org/10.1101/657999.
  • Göbel J, Motori E, Bergami M. Spatiotemporal control of mitochondrial network dynamics in astroglial cells. Biochem Biophys Res Commun(2018); 500:17-25.
  • Motori, E.#, Puyal, J., Toni, N., Ghanem, A., Angeloni, C., Malaguti, M., Cantelli-Forti, G., Berninger, B., Conzelmann, K.K., Götz, M., Winklhofer, K., Hrelia, S.*, and Bergami, M.*,# Inflammation-induced alteration of astrocyte mitochondrial dynamics requires autophagy for mitochondrial network maintenance. Cell Metab (2013); 18, 844-859. #co-corresponding; *equal contribution.

Overview of publications generated during the current funding period (1/2023-12/2025) with CMMC affiliation

For further publications, please use the - pubmed_Bergami

Prof. Dr. Matteo Bergami CMMC Cologne
Prof. Dr. Matteo Bergami

CECAD Cologne

CMMC - PI - A 02

+49 221 478 84250

+49 221 478 78910

CECAD Cologne

Joseph-Stelzmann-Str. 26

50931 Cologne

https://bergami-lab.com/

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Dr. Elisa Motori CMMC Cologne
Dr. Elisa Motori

Institute of Biochemistry

CMMC - Co-PI - A 02