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This review compiles the roles of TME cells and molecules in driving malignant progression and metastasis, highlights signaling pathways that mediate tumor–TME crosstalk, and outlines therapeutic implications for targeting molecular and cellular components to control GC aggressiveness.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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is the tumor microenvironment (TME) important in gastric cancer progression?","Question",{"text":63,"@type":64},"The TME regulates tumor-cell functions and promotes aggressiveness and dissemination through interactions among multiple cellular and molecular components, including immune cells, fibroblasts, and vasculature-related cells.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Which kinds of TME components does the review focus on?",{"text":68,"@type":64},"The review summarizes roles of various TME cells and molecules, emphasizing stromal components such as cancer-associated fibroblasts, along with signaling pathways that mediate tumor–TME interactions.",{"name":70,"@type":61,"acceptedAnswer":71},"How do signaling pathways and molecular mechanisms influence metastasis in gastric cancer?",{"text":72,"@type":64},"Signaling pathways mediate crosstalk between cancer cells and different TME components, strengthening the progressive and metastatic potential and supporting 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Microenvironment  \nTasuku Matsuoka 1,2 and Masakazu Yashiro 1,2, *  \nCitation: Matsuoka, T.; Yashiro, M. Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment. Int. J. Mol. Sci. 2024, 25, 11735. [https://](https://)  \n[doi.org/10.3390/ijms252111735](doi.org/10.3390/ijms252111735)[ ](doi.org/10.3390/ijms252111735)Academic Editor: Hidekazu Suzuki  \nReceived: 31 August 2024  \nRevised: 23 October 2024  \nAccepted: 30 October 2024  \nPublished: 31 October 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 5458585, Japan; [t22738q@omu.ac.jp](t22738q@omu.ac.jp)  \n[2](2 Institute of Medical Genetics)[ Institute of Medical Genetics](2 Institute of Medical Genetics), [Osaka Metropolitan University](Osaka Metropolitan University), [1-4-3 Asahi-machi](1-4-3 Asahi-machi), [Abeno-ku](Abeno-ku), Osaka 5458585, Japan  \n* Correspondence: [i21496f@omu.ac.jp](i21496f@omu.ac.jp); Tel.: +81-6-6645-3935  \nAbstract: Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of GC, and progress in the development of effective anti-GC drugs has been insufficient. The tumor microenvironment (TME) regulates various functions of tumor cells, and interactions between the cellular and molecular components of the TME—e.g., inflammatory cells, fibroblasts, vasculature cells, and innate and adaptive immune cells—promote the aggressiveness of cancer cells and dissemination to distant organs. This review summarizes the roles of various TME cells and molecules in regulating the malignant progression and metastasis of GC. We also address the important roles of signaling pathways in mediating the interaction between cancer cells and the different components of the GC TME. Finally, we discuss the implications of these molecular mechanisms for developing novel and effective therapies targeting molecular and cellular components of the GC TME to control the malignant progression of GC.  \nKeywords: gastric cancer; tumor microenvironment; signaling pathway; immune tolerance; microbiota  \n1. Introduction  \nThe tumor stroma is composed of various cellular and non-cellular factors, such as fibroblasts, vascular endothelial cells, immune cells, cytokines, and the extracellular matrix (ECM), and each of these factors influences the others to create a complex tumor microenvironment (TME) [1] . The molecular mechanisms underlying the involvement of the TME in cancer progression were unknown for many years. However, recent technological innovations such as single-cell analysis technologies and developments in simulation technology based on mathematical science have revealed several interactions between immune cells and stromal cells in tumor tissue. Mechanisms of tumor growth induction through organ-related factors including the bacterial flora have also been elucidated, highlighting the importance of the TME in the aggressiveness, invasion, dissemination, and colonization of cancer cells to secondary foci [2] . In this review, we summarize the current findings on the molecular mechanisms of the involvement of TME in various stages of the malignant progression of gastric cancer (GC). We also address how various signaling pathways interact with the GC TME and contribute to cancer’s progressive and metastatic potential. Finally, we discuss challenges in the targeting of TME components for targeting TME components to improve therapeutic ou","cbCaif9x3COoKIYm","https://ap.wps.com/l/cbCaif9x3COoKIYm","pdf",2453243,33,"English","# Abstract\n# 1. Introduction\n# 2. Component of the TME in GC\n## 2.1. Stromal Cells\n## 2.1.1. Cancer-Associated Fibroblasts (CAFs)","[{\"question\":\"Why is the tumor microenvironment (TME) important in gastric cancer progression?\",\"answer\":\"The TME regulates tumor-cell functions and promotes aggressiveness and dissemination through interactions among multiple cellular and molecular components, including immune cells, fibroblasts, and vasculature-related cells.\"},{\"question\":\"Which kinds of TME components does the review focus on?\",\"answer\":\"The review summarizes roles of various TME cells and molecules, emphasizing stromal components such as cancer-associated fibroblasts, along with signaling pathways that mediate tumor–TME interactions.\"},{\"question\":\"How do signaling pathways and molecular mechanisms influence metastasis in gastric cancer?\",\"answer\":\"Signaling pathways mediate crosstalk between cancer cells and different TME components, strengthening the progressive and metastatic potential and supporting TME-driven mechanisms across stages of malignant progression.\"}]","Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment - review | PDF",1789993628,83]