Kovaleva Olga, Sorokin Maxim, Egorova Anastasija, Petrenko Anatoly, Shelekhova Ksenya, Gratchev Alexei
Laboratory for Tumor Stromal Cell Biology, Institute of Carcinogenesis, Nikolaj Nikolajevich (N.N.) Blokhin National Medical Research Center of Oncology, Moscow, Russia.
Department of Pathology, Clinical Research and Practical Center for Specialized Oncological Care, St. Petersburg, Russia.
Front Oncol. 2023 Feb 23;13:1078029. doi: 10.3389/fonc.2023.1078029. eCollection 2023.
Tumor cells communication with tumor associated macrophages is a highly important factor of tumor malignant potential development. For a long time, studies of this interaction were focused on a cytokine- and other soluble factors -mediated processes. Discovery of exosomes and regulatory RNAs as their cargo opened a broad field of research. Non-coding RNAs (ncRNAs) were demonstrated to contribute significantly to the development of macrophage phenotype, not only by regulating expression of certain genes, but also by providing for feedback loops of macrophage activation. Being a usual cargo of macrophage- or tumor cell-derived exosomes ncRNAs provide an important mechanism of tumor-stromal cell interaction that contributes significantly to the pathogenesis of various types of tumors. Despite the volume of ongoing research there are still many gaps that must be filled before the practical use of ncRNAs will be possible. In this review we discuss the role of regulatory RNAs in the development of macrophage phenotype. Further we review recent studies supporting the hypothesis that macrophages may affect the properties of tumor cells and vice versa tumor cells influence macrophage phenotype by miRNA and lncRNA transported between these cells by exosomes. We suggest that this mechanism of tumor cell - macrophage interaction is highly promising for the development of novel diagnostic and therapeutic strategies, though many problems are still to be solved.
肿瘤细胞与肿瘤相关巨噬细胞之间的通讯是肿瘤恶性潜能发展的一个非常重要的因素。长期以来，对这种相互作用的研究主要集中在细胞因子和其他可溶性因子介导的过程。外泌体及其携带的调节性RNA的发现开辟了一个广阔的研究领域。非编码RNA（ncRNAs）不仅通过调节某些基因的表达，还通过提供巨噬细胞激活的反馈环，被证明对巨噬细胞表型的发展有显著贡献。作为巨噬细胞或肿瘤细胞来源外泌体的常见成分，ncRNAs提供了一种肿瘤-基质细胞相互作用的重要机制，对各种类型肿瘤的发病机制有显著贡献。尽管正在进行大量研究，但在ncRNAs能够实际应用之前，仍有许多空白需要填补。在这篇综述中，我们讨论调节性RNA在巨噬细胞表型发展中的作用。此外，我们回顾了最近的研究，这些研究支持巨噬细胞可能影响肿瘤细胞特性，反之肿瘤细胞通过外泌体在这些细胞之间运输的miRNA和lncRNA影响巨噬细胞表型的假说。我们认为，这种肿瘤细胞-巨噬细胞相互作用机制对新型诊断和治疗策略的开发具有很大的前景，尽管仍有许多问题有待解决。
