Harrell Carl Randall, Djonov Valentin, Volarevic Vladislav
Regenerative Processing Plant, Palm Harbor, Florida, United States of America.
Institute of Anatomy, University of Bern, Bern, Switzerland.
Histol Histopathol. 2023 Dec;38(12):1373-1379. doi: 10.14670/HH-18-633. Epub 2023 May 26.
Mesenchymal stem cell (MSC)-dependent biological effects in the tumor microenvironment mainly rely on the activity of MSC-sourced microRNAs (MSC-miRNAs) which modulate protein synthesis in target tumor cells, endothelial cells and tumor-infiltrated immune cells, regulating their phenotype and function. Several MSC-sourced miRNAs (miR-221, miR-23b, miR-21-5p, miR-222/223, miR-15a miR-424, miR-30b, miR-30c) possess tumor-promoting properties and are able to enhance viability, invasiveness and metastatic potential of malignant cells, induce proliferation and sprouting of tumor endothelial cells and suppress effector functions of cytotoxic tumor-infiltrated immune cells, crucially contributing to the rapid growth and progression of tumor tissue. On the contrary, MSCs also produce "anti-tumorigenic" miRNAs (miR-100, miR-222-3p, miR-146b miR-302a, miR-338-5p, miR-100-5p and miR-1246) which suppress tumor growth and progression by: Up-regulating expression of chemoresistance-related genes in tumor cells, by suppressing neo-angiogenesis and by inducing generation of tumorotoxic phenotypes in tumor-infiltrated lymphocytes. In this review article, we summarize the current knowledge about molecular mechanisms that are responsible for MSC-miRNA-dependent alterations of intracellular signaling in tumor and immune cells and we discuss different insights regarding the therapeutic potential of MSC-derived miRNAs in cancer treatment.
间充质干细胞（MSC）在肿瘤微环境中产生的生物学效应主要依赖于源自MSC的微小RNA（MSC-miRNA）的活性，这些微小RNA可调节靶肿瘤细胞、内皮细胞和肿瘤浸润免疫细胞中的蛋白质合成，从而调控它们的表型和功能。几种源自MSC的微小RNA（miR-221、miR-23b、miR-21-5p、miR-222/223、miR-15a、miR-424、miR-30b、miR-30c）具有促肿瘤特性，能够增强恶性细胞的活力、侵袭性和转移潜能，诱导肿瘤内皮细胞的增殖和芽生，并抑制细胞毒性肿瘤浸润免疫细胞的效应功能，对肿瘤组织的快速生长和进展起关键作用。相反，MSC也会产生“抗肿瘤”微小RNA（miR-100、miR-222-3p、miR-146b、miR-302a、miR-338-5p、miR-100-5p和miR-1246），这些微小RNA通过以下方式抑制肿瘤生长和进展：上调肿瘤细胞中化疗耐药相关基因的表达、抑制新生血管生成以及诱导肿瘤浸润淋巴细胞产生肿瘤毒性表型。在这篇综述文章中，我们总结了目前关于负责肿瘤细胞和免疫细胞中依赖于MSC-miRNA的细胞内信号改变的分子机制的知识，并讨论了关于源自MSC的微小RNA在癌症治疗中的治疗潜力的不同见解。
