In search of definitions: Cancer‐associated fibroblasts and their markers

• Published in: International journal of cancer Vol. 146; no. 4; pp. 895 - 905
• Main Authors: Nurmik, Martin, Ullmann, Pit, Rodriguez, Fabien, Haan, Serge, Letellier, Elisabeth
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15-02-2020; Wiley Subscription Services, Inc
• Subjects: Actin; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biomarkers, Tumor - metabolism; Cancer; Cancer-Associated Fibroblasts - drug effects; Cancer-Associated Fibroblasts - metabolism; cancer‐associated fibroblasts; Cell Separation - methods; Disease Progression; Drug resistance; Fibroblast activation protein; fibroblast heterogeneity; fibroblast markers; Fibroblasts; Flow Cytometry - methods; Humans; Medical research; Mini Review; Mini Reviews; Muscles; Neoplasm Invasiveness - pathology; Neoplasms - drug therapy; Neoplasms - pathology; Smooth muscle; Standardization; Subpopulations; Tumor Microenvironment; cancer-associated fibroblasts; tumor microenvironment; fibroblast heterogeneity; fibroblast markers
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.32193

The tumor microenvironment has been identified as one of the driving factors of tumor progression and invasion. Inside this microenvironment, cancer‐associated fibroblasts (CAFs), a type of perpetually activated fibroblasts, have been implicated to have a strong tumor‐modulating effect and play a key role in areas such as drug resistance. Identification of CAFs has typically been carried based on the expression of various “CAF markers”, such as fibroblast activation protein alpha (FAP) and alpha smooth muscle actin (αSMA), which separates them from the larger pool of fibroblasts present in the body. However, as outlined in this Review, the expression of various commonly used fibroblast markers is extremely heterogeneous and varies strongly between different CAF subpopulations. As such, novel selection methods based on cellular function, as well as further characterizing research, are vital for the standardization of CAF identification in order to improve the cross‐applicability of different research studies in the field. The aim of this review is to give a thorough overview of the commonly used fibroblast markers in the field and their various strengths and, more importantly, their weaknesses, as well as to highlight potential future avenues for CAF identification and targeting.