Fibroblasts in pancreatic cancer: molecular and clinical perspectives |
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| Institution: | 1. Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, 4200-135 Porto, Portugal;2. Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology (IPATIMUP), University of Porto, 4200-135 Porto, Portugal;3. Department of Biological Sciences, Faculty of Pharmacy of the University of Porto (FFUP), Porto, Portugal;4. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands;5. Fondazione Pisana per La Scienza, Pisa, Italy;1. Vall d’Hebron Research Institute (VHIR). Universitat Autónoma de Barcelona, Barcelona, 08035, Spain;2. Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, 03010, Spain;3. Instituto de Neurosciencias CSIC-UMH, San Juan de Alicante, 03550, Spain;1. JCCU Translational Surgical Oncology (A430), German Cancer Research Center (DKFZ), Heidelberg, Germany;2. DKFZ-Hector Cancer Institute, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;3. Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;4. Department of Thoracic Surgery, The First Hospital of Jilin University, Jilin, China;5. Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany;6. Department of Personalized Oncology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany;1. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China;2. University of Chinese Academy of Sciences, Beijing, China;3. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China;4. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China;5. Aging Biomarker Consortium, China;6. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China;7. School of Life Science, Beijing Institute of Technology, Beijing, China;8. School of Life Sciences, Xiamen University, Xiamen, China;9. Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, China;10. Aging Translational Medicine Center, International Center for Aging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, China;1. Gottfried Schatz Research Center, Molecular Biology and Biochemistry, Medical University of Graz, 8010 Graz, Austria;1. Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA;2. Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN, USA;3. Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA;1. Department of Kinesiology, Faculty of Science, McMaster University, Hamilton, Ontario, Canada |
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| Abstract: | Pancreatic stellate cells (PSCs) and cancer-associated fibroblasts (CAFs) are highly abundant cells in the pancreatic tumor microenvironment (TME) that modulate desmoplasia. The formation of a dense stroma leads to immunosuppression and therapy resistance that are major causes of treatment failure in pancreatic ductal adenocarcinoma (PDAC). Recent evidence suggests that several subpopulations of CAFs in the TME can interconvert, explaining the dual roles (antitumorigenic and protumorigenic) of CAFs in PDAC and the contradictory results of CAF-targeted therapies in clinical trials. This highlights the need to clarify CAF heterogeneity and their interactions with PDAC cells. This review focuses on the communication between activated PSCs/CAFs and PDAC cells, as well as on the mechanisms underlying this crosstalk. CAF-focused therapies and emerging biomarkers are also outlined. |
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