In order for pancreatic cancer cells to survive in the hypoxic and nutrient-poor tumour microenvironment, the cancer cells undergo so-called metabolic rewiring, i.e., they pursue unorthodox strategies for nutrient acquisition and utilization.
Pancreatic stellate cells (PSCs), the stromal cells that produce the abundant extracellular matrix that is characteristic of pancreatic cancer, are suspected to play a central role in this process. At the same time, PSCs are also key to the induction of chemoresistance.
This work package focuses on the biology of PSCs, which seem to be at the nexus between metabolic rewiring and chemoresistance, and may therefore be of particular therapeutic interest as potential target cells for new therapeutic approaches aimed at interfering with cancer cell metabolism.
Experiments will be based on co-cultures of cancer cells and PSCs as well as spheroids and organoids derived from human pancreatic cancer specimens. Furthermore, the project will investigate the effects of neoadjuvant chemotherapy both on metabolic rewiring in the tumor tissue and on alterations in the systemic metabolism of the patient (in collaboration with work package 'Surgery', NorPACT-3 study).
Collaborators
Caroline Verbeke (work package “Pathology”), University of Oslo/Oslo University Hospital
Katja Benedikte Prestø Elgstøen, Oslo University Hospital
Anders Molven (work package “Animal models”), University of Bergen
Stein Kaasa (work package “Oncology”), Oslo University Hospital/University of Oslo
Chantal Pauli, University Hospital Zürich
Rainer Heuchel & Matthias Löhr, Karolinska Institute
Publications