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Review
. 2021 Sep 21;13(18):4720.
doi: 10.3390/cancers13184720.

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Paris Jabeen Asif  1   2 , Ciro Longobardi  1   2 , Michael Hahne  3 , Jan Paul Medema  1   2
Affiliations
Review

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Paris Jabeen Asif et al. Cancers (Basel). .

Abstract

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

Keywords: CAF-targeted therapy; cancer-associated fibroblast; colorectal cancer; epithelial-to-mesenchymal transition; extracellular matrix; invasion; metastasis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
ECM remodeling and EMT modulated by CAFs. CAFs can modify ECM to promote invasion and metastasis of cancer cells by: inducing matrix stiffness; creating tracks for cancer cell invasion; secreting proteases and cytokines. CAFs can also induce EMT.
See this image and copyright information in PMC

References

    1. Retsas S. Cancer and the arts: Metastasis-as perceived through the ages. ESMO Open. 2017;2:e000226. doi: 10.1136/esmoopen-2017-000226. - DOI - PMC - PubMed
    1. Attieh Y., Clark A.G., Grass C., Richon S., Pocard M., Mariani P., Elkhatib N., Betz T., Gurchenkov B., Vignjevic D.M. Cancer-associated fibroblasts lead tumor invasion through integrin-beta3-dependent fibronectin assembly. J. Cell Biol. 2017;216:3509–3520. doi: 10.1083/jcb.201702033. - DOI - PMC - PubMed
    1. Winkler J., Abisoye-Ogunniyan A., Metcalf K.J., Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat. Commun. 2020;11:5120. doi: 10.1038/s41467-020-18794-x. - DOI - PMC - PubMed
    1. Arina A., Idel C., Hyjek E.M., Alegre M.L., Wang Y., Bindokas V.P., Weichselbaum R.R., Schreiber H. Tumor-associated fibroblasts predominantly come from local and not circulating precursors. Proc. Natl. Acad. Sci. USA. 2016;113:7551–7556. doi: 10.1073/pnas.1600363113. - DOI - PMC - PubMed
    1. Sahai E., Astsaturov I., Cukierman E., DeNardo D.G., Egeblad M., Evans R.M., Fearon D., Greten F.R., Hingorani S.R., Hunter T., et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer. 2020;20:174–186. doi: 10.1038/s41568-019-0238-1. - DOI - PMC - PubMed