What is new in cancer-associated fibroblast biomarkers?

Abstract

The tumor microenvironment is one of the important drivers of tumor development. Cancer-associated fibroblasts (CAFs) are a major component of the tumor stroma and actively participate in tumor development, invasion, metastasis, drug resistance, and other biological behaviors. CAFs are a highly heterogeneous group of cells, a reflection of the diversity of their origin, biomarkers, and functions. The diversity of CAF origin determines the complexity of CAF biomarkers, and CAF subpopulations expressing different biomarkers may play contrasting roles in tumor progression. In this review, we provide an overview of these emerging CAF biomarkers and the biological functions that they suggest, which may give a better understanding of the relationship between CAFs and tumor cells and be of great significance for breakthroughs in precision targeted therapy for tumors.

Cancer-associated fibroblasts reveal aberrant DNA methylation across different types of cancer

“…While not all liver-CAF samples exhibited distinct signatures, it is conceivable that the CAF low samples encompass either less activated fibroblasts or distinct subpopulations. Previous research has identified different CAF-clusters (Yu et al, 2022; Zou et al, 2022) and it was even speculated that CAF subpopulations expressing different biomarkers might either promote or counteract tumor growth (Han et al, 2020; Zhao et al, 2023). In addition, Ma et al have recently delved into the heterogeneity of CAF subsets using single cell gene expression data across different cancer types (Ma et al, 2023).…”

“…Furthermore, analysis of methylome and transcriptome data consistently identified CAF high samples with abnormal expression, particularly in candidate CAF-markers such as RUNX3 (Koyama et al, 2023) and EDARADD (Lawrence et al, 2020). The heterogeneity in CAFs in transcriptome and DNAm might also originate from different cellular sources recruited into the CAF compartment (Zhao et al, 2023). Nevertheless, our analysis suggests that CAF-associated DNAm profiles closely resemble those of normal fibroblasts, hinting at a fibroblastoid cellular origin.…”

“…A bottleneck in the molecular characterization of CAFs is that fibroblasts generally resemble complex cell populations with striking inter- and intra-organic heterogeneity (Muhl et al, 2020). The heterogeneity of CAFs is further complicated by diverse cellular origins that can be recruited and activated during tumorigenesis, including normal-tissue associated fibroblasts (NAFs), bone marrow-derived mesenchymal stromal cells (MSCs), stellate cells, epithelial cells, and endothelial cells (Zhao et al, 2023). This heterogeneity makes it difficult to precisely define CAFs at the molecular level and may lead to a different mechanistic contribution of CAF subtypes to cancer pathophysiology (Bu et al, 2019).…”

Gelatin methacryloyl and Laponite bioink for 3D bioprinted organotypic tumor modeling

“…To what concern genes related to the activation of fibroblast into CAFs, the gene set for CAF signature was composed of COL1A1, COL1A2 [76], VEGF, TGFβ1 [77,78], fibronectin [79,80], IGF1 [81][82][83], and VIM [84,85]. In addition to these genes, CAFs also gain further secretory phenotypes and ECM production/remodeling [84].…”

“…VIM expression in CAFs from PDAC patients is associated with significantly shorter overall survival [84]. VIM expression in CAFs is related to tumorigenesis, metastasis, recurrence, drug resistance, and poor prognosis in patients with several other cancers [85].…”