cancer-associated fibroblast; hypoxia; pancreatic cancer
Abstract :
[en] Despite extensive research, the 5-year survival rate of pancreatic cancer (PDAC) patients remains at only 9%. Patients often show poor treatment response, due partly to a highly complex tumor microenvironment (TME). Cancer-associated fibroblast (CAF) heterogeneity is characteristic of the pancreatic TME, where several CAF subpopulations have been identified, such as myofibroblastic CAFs (myCAFs), inflammatory CAFs (iCAFs), and antigen presenting CAFs (apCAFs). In PDAC, cancer cells continuously adapt their metabolism (metabolic switch) to environmental changes in pH, oxygenation, and nutrient availability. Recent advances show that these environmental alterations are all heavily driven by stromal CAFs. CAFs and cancer cells exchange cytokines and metabolites, engaging in a tight bidirectional crosstalk, which promotes tumor aggressiveness and allows constant adaptation to external stress, such as chemotherapy. In this review, we summarize CAF diversity and CAF-mediated metabolic rewiring, in a PDAC-specific context. First, we recapitulate the most recently identified CAF subtypes, focusing on the cell of origin, activation mechanism, species-dependent markers, and functions. Next, we describe in detail the metabolic crosstalk between CAFs and tumor cells. Additionally, we elucidate how CAF-driven paracrine signaling, desmoplasia, and acidosis orchestrate cancer cell metabolism. Finally, we highlight how the CAF/cancer cell crosstalk could pave the way for new therapeutic strategies.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Peiffer, Raphaël; Metastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
Boumahd, Yasmine; Metastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
Gullo, Charlotte; Metastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, BelgiumMetastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
Crake, Rebekah; Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
Letellier, Elisabeth ; University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM)
Bellahcène, Akeila; Metastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
Peulen, Olivier; Metastasis Research Laboratory, GIGA-Cancer, University of Liège, 4000 Liège, Belgium
External co-authors :
yes
Language :
English
Title :
Cancer-Associated Fibroblast Diversity Shapes Tumor Metabolism in Pancreatic CancerCancer-Associated Fibroblast Diversity Shapes Tumor Metabolism in Pancreatic Cancer
Publication date :
2023
Journal title :
Cancers
ISSN :
2072-6694
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Basel, Switzerland
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