Cancer-associated fibroblasts subtypes and role in invasion and metastasis of gastric cancer

Abstract

Gastric cancer (GC) is the fifth most common malignancy and the fourth leading cause of cancerrelated death worldwide. Cancer-associated fibroblasts (CAFs), an important cell type in the tumor microenvironment, play an important role in GC development. In this review, we describe the current knowledge of CAFs' heterogeneity and their role in GC invasion and metastasis. Currently, CAF-targeted cancer therapies are being rapidly explored and developed. However, the heterogeneity of CAFs limits the application of this therapy, so it is urgent to find specific markers and divide them into different subpopulations. With the development of single-cell RNA sequencing technology, researchers have used this technology to classify CAFs in many tumors, but whether it is applicable to GC and other tumors needs further study. And we believe that this technology will be in the near future utilized to sort CAFs on the basis of different cell markers and functions, so as to target tumor-promoting CAFs and inhibit tumor progression. Targeting CAFs by cell surface markers or normalizing the activated CAFs subsets may be an effective therapy, alone or in combination with other therapeutic approaches for GC treatment. Therefore, in the coming decades, the interaction between CAFs and GC cells will be still the focus of our research.

The hidden messengers: cancer associated fibroblasts—derived exosomal miRNAs as key regulators of cancer malignancy

“…According to recent studies, CAFs can produce ECM in the TME that sustains tumors, encourages pre-tumor epithelial cell growth, expansion, and diffusion, fosters the emergence of newly malignant cells, and significantly impacts the progression of different organ tumors ( Wang Y. et al, 2022 ; Sun et al, 2022 ). Through indirect cellular contact, CAFs can also control the biological activity of other mesenchymal and tumor cells, reshape and synthesize ECM, and release many regulatory factors, which can affect the development and progression of tumors ( Zhang M. et al, 2022 ; Wu et al, 2022 ). In addition, it can reprogram lipid metabolism, release lipid metabolites, get absorbed into tumor cells, encourage migration, and so forth ( Gong et al, 2020 ).…”

“…CAFs, a diverse group of interstitial cells, can be classified into various subtypes based on the differential expression of specific biomarkers, each having unique functions and roles ( Zhang M. et al, 2022 ). Fibroblasts are usually quiescent in normal tissues but can be activated during tissue injury ( Raju et al, 2022 ).…”

Crosstalk between colorectal cancer cells and cancer-associated fibroblasts in the tumor microenvironment mediated by exosomal noncoding RNAs

“…In recent years, abundant evidence has indicated that CAFs produce tumor-supporting ECM, facilitate the growth, expansion and spread of pre-tumor epithelial cells, create a comfortable environment for emerging malignant cells, and are vital drivers of tumor progression in many organs ( 38 , 39 ). In TME, CAF can regulate the biological behavior of tumor cells and other mesenchymal cells through cell-to-cell contacts; and can effect tumorigenesis and progression via release of large amounts of regulatory factors to synthesize and remodel the ECM ( 40 , 41 ). In CRC, previous studies have showed that CAFs are the main cellular constituents of stroma associated with primary and metastatic CRC ( 42 , 43 ).…”

Molecular Insight into Gastric Cancer Invasion—Current Status and Future Directions

“…CAFs have been shown to promote cancer invasion by inducing intimate interaction with cancer cells and modulating cancer-related signaling [ 127 ]. Activated CAFs can secrete a fair lot of soluble factors, involving chemokines, cytokines such as CXCL12 (SDF1), CXCL14, IL-6, IL-23, IL-33, and ligands of epidermal growth factor receptor (EGFR), members of the vascular endothelial growth factor (VEGF) family, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), TGF-β, and insulin-like growth factor (IGF) [ 128 , 129 ]. These soluble factors can increase tumor invasion [ 130 ].…”