Team members

Neural plasticity in cancer development

We aim to understand how the nervous system innervates cancerous tumours in order to regulate their development and progression.

The functioning of the nervous system is based on highly sophisticated neural networks that are formed during fetal life and childhood. During development, neurons emit long cables, called axons, to reach their target cells and establish synaptic contacts. This process is controlled by groups of specialized cells that express guidance signals and direct axons along specific trajectories. The nerve projections thus established are maintained throughout adult life. Far from being static, they retain a degree of plasticity that allows them to reshape themselves according to our experiences or in response to diseases such as cancer. Indeed, malignant tumors are able to stimulate the regrowth of mature axons and thus promote their own innervation. The importance of this phenomenon on the evolution of the disease is only beginning to be understood: the nervous system has a protective or, on the contrary, accelerating effect on tumor development, which depends on both the type of cancer and the biochemical properties of the infiltrated axons. These results raise fundamental questions that we seek to answer:


How do axonal projections remodel as a tumor develops?

How does the combination of chemical and mechanical signals generated by the tumor control axonal growth and plasticity?
How do neurons interact with cells in the tumor microenvironment and contribute to disease progression?

Reconstruction of the innervation of a cancerous lesion in a transgenic mouse model of pancreatic ductal adenocarcinoma. The axons of the sympathetic nervous system are shown in red, the interacting surfaces with blood vessels in yellow, and the lumens of epithelial lesions in blue.

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Anaïs Bellon
INSERM researcher at the Institute of Mediterranean Neurobiology (INMED), France
Marion Benezech-Lapeyre
R&D Technician at Innate Pharma, France
Katja Burk
Group leader at the Department of Neurology, University Medical Center Göttingen, Germany
Chloé Dominici
Postdoc at the Institute for Research on Cancer and Aging (IRCAN), France
Jeremy Guillot
Postdoc at the Federal Polytechnic School of Lausanne (EPFL), Switzerland
Adrien Lucchesi
Biotechnology teacher, France
Jonathan Luchino
Health professional, France
Laura Miranda
R&D Assistant at Innate Pharma, France
Erik Mire
Group leader at the Neuroscience & Mental Health Research Institute, Cardiff University, UK
Thi-Trang Huyen Nguyen
Lecturer at the University of Science and Technology of Hanoi (USTH), Vietnam
Micaela Roque
Maturation Engineer at SATT Aquitaine, France
Theodora Velona
Postdoc at the Institute of Molecular Biology and Biotechnology (IMBB), Greece

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Neural plasticity in cancer development

3D imaging of neural network remodeling

We are studying neuronal plasticity in mouse models of pancreatic ductal adenocarcinoma (PDAC). We use 3D light sheet fluorescence microscopy to visualize in whole pancreas the architecture of neural networks and their interactions with adjacent cells and structures (blood vessels, glial cells, macrophages). We discovered that axons of the sympathetic nervous system remodel very early in the development of PDAC, emitting numerous collaterals that innervate pre-cancerous lesions and the periphery of invasive tumors (Guillot et al., 2022).

Role of axonal guidance molecules

Our previous work has highlighted the multiple roles played by guidance molecules of the Semaphorin family in the development of axonal projections (Chauvet et al., 2007; Bellon et al., 2010; Burk et al., 2017; Mire et al., 2018). The overexpression of these signals in many cancers suggests that they could contribute to tumor progression. We have already shown that Semaphorin 3E confers to cancer cells a resistance to apoptosis (Luchino et al., 2013). We are now testing the hypothesis of a role of guidance signals in the structural plasticity of adult networks and the innervation of PDAC.

Functional crosstalk between nerves and cancer

Nerves have recently emerged as new regulators of cancer progression. While in many cases, nerves stimulate tumor growth and spread, we have shown that the sympathetic nervous system has an opposite protective function against PDAC. Indeed, the selective ablation of the sympathetic innervation of the pancreas accelerates tumor progression via the reprogramming of tumor-associated macrophages (Guillot et al., 2022).