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Cited by 290Cancer Cells and MetastasisCellular Mechanics and InteractionsCell Adhesion Molecules Research

Cancer-associated fibroblasts in desmoplastic tumors: emerging role of integrins

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Zeltz, Cédric, Primac, Irina, Erusappan, Pugazendhi, Alam, Jahedul, Noel, Agnes, Gullberg, Donald·2020·Seminars in Cancer Biology
DOI 10.1016/j.semcancer.2019.08.004
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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.

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Crossref · 10.1016/j.semcancer.2019.08.004

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  • CAFs produce matrix-crosslinking enzymes and, together with force-mediated ECM remodelling, these contribute to increased stiffness of tumour tissue.

    “CAFs also produce matrix-crosslinking enzymes and, together with force-mediated ECM remodelling (reviewed in detail85,86), these contribute to the increased stiffness of tumour tissue87–89.”

    From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [86]

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Authors
Zeltz, C., Primac, I., Erusappan, P., Alam, J., Noel, A., & Gullberg, D.
Affiliations
  • University Health Network (CA)
  • University of Liège (BE)
  • Oslo University Hospital (NO)
  • University of Bergen (NO)
Corresponding author
Gullberg, Donald
ORCID
Venue
Seminars in Cancer Biology
Publisher
Elsevier BV
Published
2020-05
Volume
62
Pages
166-181
ISSN
1044-579X (ISSN-L)
DOI
10.1016/j.semcancer.2019.08.004
OpenAlex
W2968449628
Cited by
290
References
16
Citations by year
2026: 15 · 2025: 42 · 2024: 41 · 2023: 58 · 2022: 57 · 2021: 53 · 2020: 22 · 2019: 2
FWCI
3.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Seminars in Cancer Biology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
  • ORBi (University of Liège) (submittedVersion, other-oa)
Funders
  • Direktoratet for internasjonalisering og kvalitetsutvikling i høgare utdanning (PNA-2014/10057)
  • FP7 People: Marie-Curie Actions (316610)
  • Norges Forskningsråd (223250)
  • Université de Liège
  • Fonds Spéciaux de Recherche
  • Senter for Internasjonalisering av Utdanning
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
cancer-associated fibroblasts, desmoplasia, tumor microenvironment, integrins, integrin α11β1, cell-matrix interactions, extracellular matrix, tumor stroma, breast cancer, lung cancer, pancreatic cancer, chemoresistance, paracrine signaling, tumor-stroma interactions, collagen
MeSH terms
Cancer-Associated Fibroblasts, Animals, Cell Transformation, Neoplastic, Disease Susceptibility, Fibroblasts, Humans, Neoplasms, Connective Tissue, Organ Specificity, Biomarkers, Tumor, Integrins, Tumor Microenvironment

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