The role of cancer-associated fibroblasts in tumorigenesis of gastric cancer

Abstract

Despite advances in anticancer therapy, the prognosis of gastric cancer (GC) remains unsatisfactory. Research in recent years has shown that the malignant behavior of cancer is not only attributable to tumor cells but is partly mediated by the activity of the cancer stroma and controlled by various molecular networks in the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are one of the most abundant mesenchymal cell components of the stroma and extensively participate in the malignant development of GC malignancy. CAFs modulate the biological properties of tumor cells in multiple ways, including the secretion of various bioactive molecules that have effects through paracrine and autocrine signaling, the release of exosomes, and direct interactions, thereby affecting GC initiation and development. However, there is marked heterogeneity in the cellular origins, phenotypes, and functions of CAFs in the TME of GC. Furthermore, variations in factors, such as proteins, microRNAs, and lncRNAs, affect interactions between CAFs and GC cells, although, the potential molecular mechanisms are still poorly understood. In this review, we aim to describe the current knowledge of the cellular features and heterogeneity of CAFs and discuss how these factors are regulated in CAFs, with a focus on how they affect GC biology. This review provides mechanistic insight that could inform therapeutic strategies and improve the prognosis of GC patients.

RETRACTED: Differential genetic mutations and immune cell infiltration in high‐ and low‐risk STAD: Implications for prognosis and immunotherapy efficacy

“…The complexity of gastric cancer arises not only from its biological heterogeneity but also from its intricate interactions with the tumour microenvironment (TME) 7,8 . Recent studies have emphasized the pivotal role of the TME in tumorigenesis, disease progression and therapeutic response, highlighting the intricate interplay between cancer cells and their surroundings 9–11 …”

“…7,8 Recent studies have emphasized the pivotal role of the TME in tumorigenesis, disease progression and therapeutic response, highlighting the intricate interplay between cancer cells and their surroundings. [9][10][11] Among the diverse components of the TME, the immune microenvironment has become a focal point of research interest. 12,13 Comprising a diverse array of immune cells, including T lymphocytes, B cells, natural killer (NK) cells, macrophages and dendritic cells (DCs), 14,15 the immune microenvironment plays a dual role in cancer, acting as defenders against tumorigenesis and as enablers promoting tumour progression and metastasis.…”

Targeting GPC3 high cancer-associated fibroblasts sensitizing the PD-1 blockage therapy in gastric cancer

“…By releasing a variety of cytokines, they communicate with each other under the action of various signal pathways. This dynamic network can recruit and transform cells, thus forming a microenvironment that supports tumour growth [ 19 ]. Among them, CAFs play an essential role in the occurrence and development of gastric cancer, because they are involved in the release of a variety of cytokines and are widely associated with inflammatory cells, nerve cells and vascular endothelial cells [ 20 ].…”

Circulating tumour cells in gastrointestinal cancers: food for thought?

“…In GI cancers, CAFs constitute a significant component in the stroma and their implication in metastasis, through various mechanisms, has been reported [78][79][80]. CAFs activate CXCL12/ CXCR4 axis by integrin β1 clustering on the cell surface, enabling GC cell invasion [81].…”