Tumor microenvironment in gastric cancers.

文献信息

DOI	10.1111/cas.14521
PMID	32519436
期刊	Cancer science
影响因子	4.3
JCR 分区	Q2
发表年份	2020
被引次数	182
关键词	癌相关成纤维细胞（CAFs）, 肿瘤相关巨噬细胞（TAMs）, 内皮细胞, 胃癌, 胃泌素
文献类型	Journal Article, Review
ISSN	1347-9032
页码	2696-2707
期号	111(8)
作者	Yukiko Oya, Yoku Hayakawa, Kazuhiko Koike

一句话小结

肿瘤微环境中多种细胞类型通过分泌分子促进癌细胞的生长与扩展，尤其是成纤维细胞、免疫细胞和内皮细胞的相互作用在胃癌发展中起关键作用。该研究揭示了肿瘤相关细胞的异质性及其在肿瘤进展中的双重角色，为未来的癌症治疗策略提供了新的靶点。

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摘要

肿瘤微环境促进癌细胞的生长和扩展。肿瘤微环境中涉及多种细胞类型，如炎症细胞、成纤维细胞、神经细胞和血管内皮细胞。这些基质细胞通过释放各种分子来促进肿瘤生长，这些分子可以直接激活癌细胞中的生长信号或重塑周围区域。本文综述了在肿瘤微环境中相互作用的最新研究进展，特别是与癌症相关的成纤维细胞（CAFs）、免疫细胞和内皮细胞的相互作用，尤其是在小鼠胃癌模型中建立的研究成果。在小鼠中，胃基质中的肌成纤维细胞分泌R-spondin，支持正常的胃干细胞。大多数CAFs以旁分泌的方式促进肿瘤生长，但CAFs群体在功能和来源上似乎是异质的，既包括促进肿瘤的群体，也包括抑制肿瘤的群体。在免疫细胞群体中，肿瘤相关的巨噬细胞，包括M1和M2巨噬细胞，以及髓源抑制细胞（MDSCs），据报道通过分泌可溶性因子或调节免疫反应直接或间接促进胃肿瘤发生。内皮细胞或血管不仅为肿瘤提供养分，还通过分泌趋化因子或细胞因子与癌症干细胞和免疫细胞相互作用，并充当癌症微环境。理解肿瘤微环境内的这些相互作用将有助于揭示新的治疗靶点。

英文摘要

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.

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主要研究问题

核心洞察

研究背景和目的

胃癌的发生与肿瘤微环境密切相关，肿瘤微环境不仅促进癌细胞的生长，还影响免疫反应。本文综述了肿瘤微环境中各种细胞类型（如癌相关成纤维细胞、免疫细胞和内皮细胞）在胃癌中的作用，重点介绍了小鼠胃癌模型中的最新研究进展，以期为新的治疗靶点的发现提供依据。

主要方法/材料/实验设计

本研究采用文献综述的方法，整合了小鼠模型中的实验结果，分析了肿瘤微环境中各类细胞的相互作用。以下是技术路线的流程图：

关键结果和发现

癌相关成纤维细胞（CAFs）：CAFs在肿瘤微环境中起着重要作用，具有促进肿瘤生长和转移的功能。不同亚群的CAFs在肿瘤进展中具有异质性，既有促进肿瘤的功能，也有抑制肿瘤的潜力。
免疫细胞：肿瘤相关巨噬细胞（TAMs）在肿瘤微环境中占据重要位置，M1型巨噬细胞具有抗肿瘤作用，而M2型则促进肿瘤生长。MDSCs通过抑制T细胞活性，进一步促进肿瘤发展。
内皮细胞：内皮细胞不仅为肿瘤提供营养，还通过分泌趋化因子和细胞因子与癌细胞及免疫细胞相互作用，形成癌症小环境。

主要结论/意义/创新性

本研究揭示了胃癌微环境中不同细胞类型的相互作用及其对肿瘤发展的影响，强调了CAFs、免疫细胞和内皮细胞在肿瘤微环境中的多重作用。这些发现为开发新的治疗策略提供了潜在靶点，尤其是在靶向肿瘤微环境方面。

研究局限性和未来方向

尽管本研究提供了对肿瘤微环境的深入理解，但当前的小鼠模型大多未能发展为侵袭性或转移性癌症。未来研究应致力于建立更符合人类病理特征的动物模型，并探索针对肿瘤微环境的治疗策略，以改善胃癌的治疗效果。

参考文献

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引用本文的文献

Tumor microenvironment in gastric cancers. - Yukiko Oya;Yoku Hayakawa;Kazuhiko Koike - Cancer science (2020)
Stromal Protein-Mediated Immune Regulation in Digestive Cancers. - Pia Gamradt;Christelle De La Fouchardière;Ana Hennino - Cancers (2021)
Dysregulated Immune Responses by ASK1 Deficiency Alter Epithelial Progenitor Cell Fate and Accelerate Metaplasia Development during H. pylori Infection. - Yoku Hayakawa;Yoshihiro Hirata;Masahiro Hata;Mayo Tsuboi;Yukiko Oya;Ken Kurokawa;Sohei Abe;Junya Arai;Nobumi Suzuki;Hayato Nakagawa;Hiroaki Fujiwara;Keisuke Tateishi;Shin Maeda;Kazuhiko Koike - Microorganisms (2020)
Cancer-associated fibroblasts: overview, progress, challenges, and directions. - Qinrong Ping;Ruping Yan;Xin Cheng;Wenju Wang;Yiming Zhong;Zongliu Hou;Yunqiang Shi;Chunhui Wang;Ruhong Li - Cancer gene therapy (2021)
Cancer-associated cells release citrate to support tumour metastatic progression. - Konstantin Drexler;Katharina M Schmidt;Katrin Jordan;Marianne Federlin;Vladimir M Milenkovic;Gerhard Liebisch;Anna Artati;Christian Schmidl;Gregor Madej;Janina Tokarz;Alexander Cecil;Wolfgang Jagla;Silke Haerteis;Thiha Aung;Christine Wagner;Maria Kolodziejczyk;Stefanie Heinke;Evan H Stanton;Barbara Schwertner;Dania Riegel;Christian H Wetzel;Wolfgang Buchalla;Martin Proescholdt;Christoph A Klein;Mark Berneburg;Hans J Schlitt;Thomas Brabletz;Christine Ziegler;Eric K Parkinson;Andreas Gaumann;Edward K Geissler;Jerzy Adamski;Sebastian Haferkamp;Maria E Mycielska - Life science alliance (2021)
Progress and Challenges of Predictive Biomarkers for Immune Checkpoint Blockade. - Yanna Lei;Xiaoying Li;Qian Huang;Xiufeng Zheng;Ming Liu - Frontiers in oncology (2021)
Potential role of mitochondria in gastric cancer detection: Fission and glycolysis. - Hang Yang;Yan Li;Bing Hu - Oncology letters (2021)
Tumor-Associated Macrophages and Inflammatory Microenvironment in Gastric Cancer: Novel Translational Implications. - Karim Rihawi;Angela Dalia Ricci;Alessandro Rizzo;Stefano Brocchi;Giovanni Marasco;Luigi Vincenzo Pastore;Fabiola Lorena Rojas Llimpe;Rita Golfieri;Matteo Renzulli - International journal of molecular sciences (2021)
SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma. - Wenping Ma;Kenan Zhang;Zhaoshi Bao;Tao Jiang;Ying Zhang - Frontiers in immunology (2021)
The Sensitivity Prediction of Neoadjuvant Chemotherapy for Gastric Cancer. - Juan Sun;Xianze Wang;Zimu Zhang;Ziyang Zeng;Siwen Ouyang;Weiming Kang - Frontiers in oncology (2021)

... (172 更多篇文献)

Tumor microenvironment in gastric cancers. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​