Tumor microenvironment in gastric cancers

Abstract

The tumor microenvironment favors the growth and expansion of cancer cells. Many cell types are involved in the tumor microenvironment such as inflammatory cells, fibroblasts, nerves, and vascular endothelial cells. These stromal cells contribute to tumor growth by releasing various molecules to either directly activate the growth signaling in cancer cells or remodel surrounding areas. This review introduces recent advances in findings on the interactions within the tumor microenvironment such as in cancer‐associated fibroblasts (CAFs), immune cells, and endothelial cells, in particular those established in mouse gastric cancer models. In mice, myofibroblasts in the gastric stroma secrete R‐spondin and support normal gastric stem cells. Most CAFs promote tumor growth in a paracrine manner, but CAF population appears to be heterogeneous in terms of their function and origin, and include both tumor‐promoting and tumor‐restraining populations. Among immune cell populations, tumor‐associated macrophages, including M1 and M2 macrophages, and myeloid‐derived suppressor cells (MDSCs), are reported to directly or indirectly promote gastric tumorigenesis by secreting soluble factors or modulating immune responses. Endothelial cells or blood vessels not only fuel tumors with nutrients, but also interact with cancer stem cells and immune cells by secreting chemokines or cytokines, and act as a cancer niche. Understanding these interactions within the tumor microenvironment would contribute to unraveling new therapeutic targets.

Cancer-associated fibroblasts: overview, progress, challenges, and directions

“…According to their different functions in tumorigenesis and development, CAFs can be divided into two subpopulations: cancer-promoting CAFs and cancer-restraining CAFs (Fig. 1C, D) [79,80]. Moreover, researchers used singlecell RNA and protein analysis techniques to study the heterogeneity of CAFs in pancreatic ductal adenocarcinoma models, and divided CAFs from pancreatic cancer into epithelial-to-mesenchymal transition (EMT-CAFs) and proliferative (PRO-CAFs) subpopulations.…”

Cancer-associated cells release citrate to support tumour metastatic progression

“…To complete these studies, we have assessed pmCiC expression in cancer cells and cancer-associated stromal cells of human breast, gastric and pancreatic tissues ( Fig 6G ). The highest expression of pmCiC in stromal cells was observed in gastric and pancreatic cancers known to intensively produce desmoplastic stroma as compared with other cancer types ( Hosein et al, 2020 ; Oya et al, 2020 ). Therefore, targeting pmCiC might have an effect not only on cancer cells but also on the tumour’s “infrastructure” (supporting cells).…”

Stromal Protein-Mediated Immune Regulation in Digestive Cancers

“…The stromal TME is composed of non-cancerous cells including immune cells (e.g., lymphocytes, macrophages, and myeloid-derived suppressor cells (MDSCs)), vascular and neural structures, as well as cancer-associated fibroblasts (CAFs) [ 12 , 13 ]. The cellular composition and differentiation of the TME is complex and has been extensively reviewed elsewhere [ 14 , 15 , 16 ]. In addition to the cellular compartment, the TME comprises a large amount of acellular components: the tumor-associated extracellular matrix (ECM), which consists of a complex meshwork of structural and regulatory proteins [ 17 ].…”