Zheng Ping, Li Wei
Department of Laboratory Medicine, The First People's Hospital of Lianyungang, Lianyungang, China.
Center of Research Laboratory, The First People's Hospital of Lianyungang, Lianyungang, China.
Front Oncol. 2020 Oct 9;10:571516. doi: 10.3389/fonc.2020.571516. eCollection 2020.
Tumor microenvironment (TME) consisting of distinct cell types including stromal cells and immune cells has recently emerged as a pivotal player in tumor development and progression. Mesenchymal stromal cells (MSCs) and tumor-associated macrophages (TAMs) are two representative cells in the TME with plastic properties. This review will focus on the evolution of phenotypes and functions of either MSCs or TAMs, which is "educated" by the TME, as well as interactions between MSCs and TAMs contributing to the distinct stages of tumor biology in gastric cancer. MSCs exert immunoregulatory effects on macrophages and polarize them toward M2-like TAMs, via cell-cell contact and paracrine or extracellular vesicle (EV) transfer mechanism. In turn, M2-TAMs modulate the transition of "naive" MSCs into tumor-derived MSCs, which possess a more potent pro-tumor role than the parent. Moreover, the cross talk between MSCs and TAMs could contribute to cancer biology by inducing the EMT process, metastasis, immune invasion, and immunotherapy resistance in cancer cells. However, molecular mechanisms underlying interactions between MSCs and TAMs in gastric cancer progression need to be thoroughly elucidated, which may provide attractive targets for making promising novel strategies for gastric cancer therapy.
由包括基质细胞和免疫细胞在内的不同细胞类型组成的肿瘤微环境（TME），最近已成为肿瘤发生和发展的关键因素。间充质基质细胞（MSCs）和肿瘤相关巨噬细胞（TAMs）是TME中具有可塑性的两种代表性细胞。本综述将聚焦于受TME “驯化” 的MSCs或TAMs的表型和功能演变，以及MSCs与TAMs之间的相互作用对胃癌肿瘤生物学不同阶段的影响。MSCs通过细胞间接触、旁分泌或细胞外囊泡（EV）转运机制对巨噬细胞发挥免疫调节作用，并使其向M2样TAMs极化。反过来，M2-TAMs调节 “幼稚” MSCs向肿瘤来源的MSCs转变，后者比其母体具有更强的促肿瘤作用。此外，MSCs与TAMs之间的相互作用可通过诱导癌细胞的上皮-间质转化（EMT）过程、转移、免疫侵袭和免疫治疗抵抗来影响癌症生物学。然而，MSCs与TAMs在胃癌进展过程中相互作用的分子机制仍需深入阐明，这可能为制定有前景的胃癌治疗新策略提供有吸引力的靶点。
