Targeting Tumor-Stromal Interactions in Pancreatic Cancer: Impact of Collagens and Mechanical Traits
2021 (Engelska) Ingår i: Frontiers in Cell and Developmental Biology, E-ISSN 2296-634X, Vol. 9, artikel-id 787485Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]
Pancreatic ductal adenocarcinoma (PDAC) has one of the worst outcomes among cancers with a 5-years survival rate of below 10%. This is a result of late diagnosis and the lack of effective treatments. The tumor is characterized by a highly fibrotic stroma containing distinct cellular components, embedded within an extracellular matrix (ECM). This ECM-abundant tumor microenvironment (TME) in PDAC plays a pivotal role in tumor progression and resistance to treatment. Cancer-associated fibroblasts (CAFs), being a dominant cell type of the stroma, are in fact functionally heterogeneous populations of cells within the TME. Certain subtypes of CAFs are the main producer of the ECM components of the stroma, with the most abundant one being the collagen family of proteins. Collagens are large macromolecules that upon deposition into the ECM form supramolecular fibrillar structures which provide a mechanical framework to the TME. They not only bring structure to the tissue by being the main structural proteins but also contain binding domains that interact with surface receptors on the cancer cells. These interactions can induce various responses in the cancer cells and activate signaling pathways leading to epithelial-to-mesenchymal transition (EMT) and ultimately metastasis. In addition, collagens are one of the main contributors to building up mechanical forces in the tumor. These forces influence the signaling pathways that are involved in cell motility and tumor progression and affect tumor microstructure and tissue stiffness by exerting solid stress and interstitial fluid pressure on the cells. Taken together, the TME is subjected to various types of mechanical forces and interactions that affect tumor progression, metastasis, and drug response. In this review article, we aim to summarize and contextualize the recent knowledge of components of the PDAC stroma, especially the role of different collagens and mechanical traits on tumor progression. We furthermore discuss different experimental models available for studying tumor-stromal interactions and finally discuss potential therapeutic targets within the stroma.
Ort, förlag, år, upplaga, sidor Frontiers Media S.A., 2021. Vol. 9, artikel-id 787485
Nyckelord [en]
collagen, extracellular matrix, mechanical traits, pancreatic cancer, PDAC—pancreatic ductal adenocarcinoma, stroma
Nationell ämneskategori
Cell- och molekylärbiologi Cancer och onkologi
Forskningsämne onkologi
Identifikatorer URN: urn:nbn:se:umu:diva-190614 DOI: 10.3389/fcell.2021.787485 ISI: 001027476700001 PubMedID: 34901028 Scopus ID: 2-s2.0-85120962866 OAI: oai:DiVA.org:umu-190614 DiVA, id: diva2:1621700
Forskningsfinansiär EU, Horisont 2020, 861196 Vetenskapsrådet, 2017-01531 Region Västerbotten, RV-930167 Region Västerbotten, VLL-832001 Cancerforskningsfonden i Norrland, LP 21-2298 Marianne och Marcus Wallenbergs Stiftelse, MMW 2020.0189 Cancerfonden, CAN 2017/332 Cancerfonden, CAN 2017/827 Cancerfonden, 20 1339 PjF 2021-12-202021-12-202025-04-24 Bibliografiskt granskad