Biomarkers for cancer-associated fibroblasts
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Biomarkers for cancer-associated fibroblasts Chencheng Han1†, Tongyan Liu1,2† and Rong Yin1,2,3,4*
Abstract Cancer-associated fibroblasts (CAFs) are the key component of tumor stromal. High heterogeneity of CAFs reflects in their origin, phenotype and function. Biological function which can be suggested by biomarkers of distinct CAF subgroups may be different, even opposite, just like water and fire. Identifying CAF subpopulations expressing different biomarkers and reconciling the relationship of the “water and fire” among distinct CAF subsets may be a breakthrough in tumor therapy. Herein, we briefly summarize the biomarkers commonly used or newly identified for distinct CAFs in terms of their features and potential clinical benefits. Keywords: Biomarker, Cancer-associated fibroblasts, Heterogeneity As the most abundant and main component in the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are generally considered as all the fibroblasts found within and surrounding tumor tissues, which are activated from normal resident tissue fibroblasts or transdifferentiated from non-fibroblastic lineage such as epithelial cells and adipocytes due to the stimulation of TME [1, 2]. CAFs were thought to be tumorpromoting by building up and remodeling extracellular matrix (ECM). However, latest study revealed the extensive inter- and intra-organ heterogeneity of fibroblasts in the physiological context [3], and several preclinical studies attempted to target CAFs directly in mouse models also failed [4, 5]. These evidences suggest an obvious heterogeneity of CAFs which may harbor both tumor-promoting and anti-tumor properties. Traditional CAF biomarkers such as α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), S100A4, * Correspondence: [email protected] † Chencheng Han and Tongyan Liu contributed equally to this work. 1 Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China 2 Department of Science and technology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China Full list of author information is available at the end of the article
platelet-derived growth factor receptors (PDGFRα/β) or vimentin have been well-studied despite none of them are specific to CAFs (Table 1) [6]. Moreover, increasing CAF subsets with distinct biomarkers expression and different cellular functions have been identified recently. We here briefly outline the biomarkers for identifying CAF heterogeneity and potential therapeutic targets.
CAFs isolation and characterization CAFs can be easily digested and cultured on plastic flasks, whereas other types of cells not, which is the basis of CAFs isolation [7]. Briefly, obtained tumor tissues are minc
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