title: Carcinoma-associated fibroblasts provide operational flexibility in metastasis.
abstract: Malignant cancer cells do not act as lone wolves to achieve metastasis, as they exist within a complex ecosystem consisting of an extracellular matrix scaffold populated by carcinoma-associated fibroblasts (CAFs), endothelial cells and immune cells. We recognize local (primary tumor) and distant ecosystems (metastasis). CAFs, also termed myofibroblasts, may have other functions in the primary tumor versus the metastasis. Cellular origin and tumor heterogeneity lead to the expression of specific markers. The molecular characteristics of a CAF remain in evolution since CAFs show operational flexibility. CAFs respond dynamically to a cancer cell's fluctuating demands by shifting profitable signals necessary in metastasis. Local, tissue-resident fibroblasts and mesenchymal stem cells (MSCs) coming from reservoir sites such as bone marrow and adipose tissue are the main progenitor cells of CAFs. CAFs may induce awakening from metastatic dormancy, a major cause of cancer-specific death. Cancer management protocols influence CAF precursor recruitment and CAF activation. Since CAF signatures represent early changes in metastasis, including formation of pre-metastatic niches, we discuss whether liquid biopsies, including exosomes, may detect and monitor CAF reactions allowing optimized prognosis of cancer patients.
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium. Electronic address: olivier.dewever@ugent.be.
authors.forename: Olivier
authors.initials: O
authors.lastname: De Wever
authors.affiliation: Department of Pathology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Bockstal
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Mareel
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Hendrix
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Radiotherapy and Experimental Cancer Research, Ghent University Hospital, Ghent, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D002450:Cell Communication; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor
keywords: Carcinoma-associated fibroblast; Ecosystem; Exosome; Invasion; Metastasis; Myofibroblast