Cancer-associated fibroblasts in desmoplastic tumors: emerging role of integrins. (May 2020)

• Record Type: Journal Article
• Authors: Zeltz, Cédric; Primac, Irina; Erusappan, Pugazendhi; Alam, Jahedul; Noel, Agnes; Gullberg, Donald
• Is Part Of: Seminars in cancer biology. Volume 62(2020)
• Page Start: 166
• Page End: 181
• Publication Date: 2020-05
• Subjects: ABCG2 ATP binding cassette subfamily G member 2 -- ADAM12 A disintegrin and metalloproteinase domain-containing protein 12 -- αSMA alpha-smooth muscle actin -- CAFs cancer-associated fibroblasts -- CAF-S cancer-associated fibroblast subset type -- cCAFs cell cycle cancer-associated fibroblasts -- CAV1 caveolin-1 -- CD10 cluster of differentiation 10, membrane metallo-endopeptidase (MME) -- CD29 cluster of differentiation 29, integrinβ1 -- CD49c cluster of differentiation 49c, integrinα3 subunit -- CD49e cluster of differentiation 49e, integrinα5 subunit -- CD51 cluster of differentiation 51, integrinαv subunit -- CD105 cluster of differentiation 105, endoglin -- CD126 cluster of differentiation 126, interleukin 6 receptor -- CLCF1 cardiotrophin-like cytokine factor 1 -- CLU clusterin -- CSC cancer stem cell -- dCAFS developmental cancer-associated fibroblasts -- dcn decorin -- DDR2 discoidin domain receptor 2 -- DPP4 dipeptidylpeptidase 4 -- ECM extracellular matrix -- EMT epithelial-mesenchymal transition -- EndoMT endothelial-mesenchymal transition -- ER estrogen receptor -- ERK extracellular signal-regulated kinase -- FAK focal adhesion kinase -- FAP fibroblast activation protein -- FGF fibroblast growth factor -- FSP-1 fibroblast specific protein-1 -- GFPT2 glutamin-fructose-6-phosphate transaminase 2 -- GLI1 glioma-associated oncogene homologue 1 -- GPR77 G protein-coupled receptor 77 -- HER2 human epidermal growth factor receptor 2 -- HGF hepatocyte growth factor -- Hh hedgehog -- iCAFS inflammatory cancer-associated fibroblasts -- IGF insulin-like growth factor -- IGFBP3 insulin-like growth factor-binding protein 3 -- IL-1 interleukin-1 -- IL-6 interleukin-6 -- IL-11 interleukin-11 -- IL-33 interleukin-33 -- IRAK-4 interleukin-1 receptor-associated kinase 4 -- KPC KrasLSL.G12D/+, p53R172 H/+, PdxCretg/+ -- LIF leukemia inhibitory factor -- LumA luminal A breast cancer subtype -- LTBP3 latent transforming growth factor Beta binding protein 3 -- LOXL1 lysyl oxidase-like 1 -- LOXL2 lysyl oxidase-like 2 -- mCAFS matrix cancer-associated fibroblasts -- MAPK mitogen-activated protein kinase -- MDSCs myeloid-derived suppressor cells -- MMTV mouse mammary tumor virus -- MRTF myocardin-related transcription factor -- MSCs mesenchymal stem cells -- myCAFS myofibroblastic cancer-associated fibroblasts -- NF normal fibroblast -- NG2 neuron-glial antigen 2 -- NSCLC non-small cell lung carcinoma -- PDAC pancreatic ductal adenocarcinoma -- PDGFRα platelet-derived growth factor receptor alpha -- PDGFRβ platelet-derived growth factor receptor beta -- pFAK phosphorylated focal adhesion kinase -- P-GP P-glycoprotein -- PyMT polyoma middle T -- PTEN phosphatase and tensin homologue -- RTKs receptor tyrosine kinases -- RTKIs receptor tyrosine kinase inhibitors -- SCC squamous cell carcinoma -- SMOi Smoothened inhibitor -- STAT3 signal transducer and activator of transcription 3 -- STC1 stanniocalcin-1 -- Taz transcriptional coactivator with PDZ-binding motif -- TAM tumor-associated macrophage -- TGF-β transforming growth factor-β -- TNBC triple negative breast cancer -- TME tumor microenvironment -- vCAFS vascular cancer-associated fibroblasts -- WISP2 WNT1- inducible signaling pathway protein2 -- YAP yes-associated protein; Tumor microenvironment -- Cancer-associated fibroblast -- Fibrosis -- TME-Mediated chemoresistance -- Integrin; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2019.08.004
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: The tumor microenvironment (TME) is a complex meshwork of extracellular matrix (ECM) macromolecules filled with a collection of cells including cancer-associated fibroblasts (CAFs), blood vessel associated smooth muscle cells, pericytes, endothelial cells, mesenchymal stem cells and a variety of immune cells. In tumors the homeostasis governing ECM synthesis and turnover is disturbed resulting in abnormal blood vessel formation and excessive fibrillar collagen accumulations of varying stiffness and organization. The disturbed ECM homeostasis opens up for new types of paracrine, cell-cell and cell-ECM interactions with large consequences for tumor growth, angiogenesis, metastasis, immune suppression and resistance to treatments. As a main producer of ECM and paracrine signals the CAF is a central cell type in these events. Whereas the paracrine signaling has been extensively studied in the context of tumor-stroma interactions, the nature of the numerous integrin-mediated cell-ECM interactions occurring in the TME remains understudied. In this review we will discuss and dissect the role of known and potential CAF interactions in the TME, during both tumorigenesis and chemoresistance-induced events, with a special focus on the "interaction landscape" in desmoplastic breast, lung and pancreatic cancers. As an example of the multifaceted mode of action of the stromal collagen receptor integrin α11β1, we will summarize our current understanding on the role of this CAF-expressed integrin in these three tumor types.