Jahangiri Babak, Khalaj-Kondori Mohammad, Asadollahi Elahe, Kian Saei Ali, Sadeghizadeh Majid
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Department of Molecular Medicine, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.
J Cell Commun Signal. 2023 Dec;17(4):1229-1247. doi: 10.1007/s12079-023-00794-3. Epub 2023 Nov 16.
Mesenchymal stem cells (MSCs) are multipotent, self-renewing stromal cells found in a variety of adult tissues. MSCs possess a remarkable ability to migrate towards tumor sites, known as homing. This homing process is mediated by various factors, including chemokines, growth factors, and extracellular matrix components present in the tumor microenvironment. MSCs release extracellular vesicles known as exosomes (MSC-Exos), which have been suggested to serve a key role in mediating a wide variety of MSC activities. Through cell-cell communication, MSC-Exos have been shown to alter recipient cell phenotype or function and play as a novel cell-free alternative for MSC-based cell therapy. However, MSC recruitment to tumors allows for their interaction with cancer cells and subsequent regulation of tumor behavior. MSC-Exos act as tumor niche modulators via transferring exosomal contents, such as specific proteins or genetic materials, to the nearby cancer cells, leading to either promotion or suppression of tumorigenesis, angiogenesis, and metastasis, depending on the specific microenvironmental cues and recipient cell characteristics. Consequently, there is still a debate about the precise relationship between tumor cells and MSC-Exos, and it is unclear how MSC-Exos impacts tumor cells. Although the dysregulation of miRNAs is caused by the progression of cancer, they also play a direct role in either promoting or inhibiting tumor growth as they act as either oncogenes or tumor suppressors. The utilization of MSC-Exos may prove to be an effective method for restoring miRNA as a means of treating cancer. This review aimed to present the existing understanding of the impact that MSC-Exos could have on cancer. To begin with, we presented a brief explanation of exosomes, MSCs, and MSC-Exos. Following this, we delved into the impact of MSC-Exos on cancer growth, EMT, metastasis, angiogenesis, resistance to chemotherapy and radiotherapy, and modulation of the immune system. Opposing effects of mesenchymal stem cells-derived exosomes on cancer cells.
间充质干细胞（MSCs）是存在于多种成人组织中的多能、自我更新的基质细胞。MSCs具有向肿瘤部位迁移的显著能力，即归巢。这种归巢过程由多种因素介导，包括肿瘤微环境中存在的趋化因子、生长因子和细胞外基质成分。MSCs释放称为外泌体的细胞外囊泡（MSC-Exos），有人认为其在介导多种MSC活性中起关键作用。通过细胞间通讯，MSC-Exos已被证明可改变受体细胞表型或功能，并作为基于MSC的细胞治疗的新型无细胞替代物发挥作用。然而，MSCs向肿瘤的募集使其能够与癌细胞相互作用并随后调节肿瘤行为。MSC-Exos通过将外泌体内容物（如特定蛋白质或遗传物质）转移到附近癌细胞，充当肿瘤微环境调节剂，根据特定的微环境线索和受体细胞特征，导致肿瘤发生、血管生成和转移的促进或抑制。因此，关于肿瘤细胞与MSC-Exos之间的确切关系仍存在争议，并且尚不清楚MSC-Exos如何影响肿瘤细胞。尽管miRNA的失调是由癌症进展引起的，但它们作为癌基因或肿瘤抑制因子，在促进或抑制肿瘤生长中也起直接作用。利用MSC-Exos可能被证明是恢复miRNA作为治疗癌症手段的有效方法。本综述旨在介绍对MSC-Exos可能对癌症产生的影响的现有认识。首先，我们对外泌体、MSCs和MSC-Exos进行了简要解释。在此之后，我们深入探讨了MSC-Exos对癌症生长、上皮-间质转化、转移、血管生成、化疗和放疗抗性以及免疫系统调节的影响。间充质干细胞衍生的外泌体对癌细胞的相反作用。
