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Exploring perineural invasion (PNI) mechanisms in Pancreatic Cancer using hyperpolarized 13C NMR

Project description

Insight into pancreatic cancer perineural invasion

Cancer cells from aggressive tumours such as pancreatic cancer can migrate and invade nerves, leading to a pathological process known as perineural invasion (PNI). PNI causes severe pain and is associated with poor prognosis and poor survival. Although PNI is poorly understood, Schwann cells are believed to interact with and become activated by cancer cells to promote PNI. Funded by the Marie Skłodowska-Curie Actions programme, the PCPNIHyp project aims to investigate the role of metabolic dysregulation caused by cancer cells in PNI. The study will identify biomarkers for early PNI diagnosis and potential therapies, leveraging advanced NMR signal-enhancement techniques by hyperpolarisation by parahydrogen-induced polarisation (PHIP) and cellular and molecular biology.

Objective

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with 5-year survival rate of less than 7%. Existing treatments are limited because 90-100% of patients develop perineural invasion (PNI). PNI is associated with severe pain, poor prognosis, poor survival, and tumor recurrence, and involves nerve invasion by cancer cells, as a result of dynamic interactions between them and other cells in the tumor microenvironment (TME). Schwann cells (SCs) are part of this TME and are activated by cancer cells to become PNI promoters. To date, the question of how metabolic dysregulation generated by cancer cells, characterized by different levels of lactate and an acidic TME drives SCs-mediated-PNI remains unanswered. Taking account that PNI is still poorly understood and that there are no PNI-targeted diagnosis methods or effective therapies, this project pursues the study of the role of metabolic alterations induced by PDAC cells on SCs, and how that drives SCs activation and PNI. To achieve this goal, nuclear magnetic resonance (NMR) mediated hyperpolarization of metabolites as contrast agents that could be used later in clinical diagnosis without adverse effects will be used. Hyperpolarization by Para-Hydrogen-Induced-Polarization (PHIP) boosts the detectable NMR and magnetic resonance image (MRI) metabolites signals by a factor of >10000, it allows obtaining precise kinetic data on metabolites’ inter-conversion on short timescales, and the insights from cells can be directly translated into in vivo studies. All of this represents an advantage over standard biological studies, which often struggle to capture these types of events. Using NMR-PHIP technology with cellular and molecular biology-based techniques on SCs-PDAC cells co-cultures and on an in vivo PNI model, this project will contribute to identifying new predictive biomarkers for future monitoring and early diagnosis of PNI, as well as to the potential development of PNI-targeted therapies.

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

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€ 189 687,36
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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