Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Adv Exp Med Biol. 2020;1234:31-42. doi: 10.1007/978-3-030-37184-5_3.
The interactions between tumor cells and the non-malignant stromal and immune cells that make up the tumor microenvironment (TME) are critical to the pathophysiology of cancer. Mesenchymal stem cells (MSCs) are multipotent stromal stem cells found within most cancers and play a critical role influencing the formation and function of the TME. MSCs have been reported to support tumor growth through a variety of mechanisms including (i) differentiation into other pro-tumorigenic stromal components, (ii) suppression of the immune response, (iii) promotion of angiogenesis, (iv) enhancement of an epithelial-mesenchymal transition (EMT), (v) enrichment of cancer stem-like cells (CSC), (vi) increase in tumor cell survival, and (vii) promotion of tumor metastasis. In contrast, MSCs have also been reported to have antitumorigenic functions including (i) enhancement of the immune response, (ii) inhibition of angiogenesis, (iii) regulation of cellular signaling, and (iv) induction of tumor cell apoptosis. Although literature supporting both arguments exists, most studies point to MSCs acting in a cancer supporting role within the confines of the TME. Tumor-suppressive effects are observed when MSCs are used in higher ratios to tumor cells. Additionally, MSC function appears to be tissue type dependent and may rely on cancer education to reprogram a naïve MSC with antitumor effects into a cancer-educated or cancer-associated MSC (CA-MSC) which develops pro-tumorigenic function. Further work is required to delineate the complex crosstalk between MSCs and other components of the TME to accurately assess the impact of MSCs on cancer initiation, growth, and spread.
肿瘤细胞与构成肿瘤微环境（TME）的非恶性基质和免疫细胞之间的相互作用对癌症的病理生理学至关重要。间充质干细胞（MSCs）是存在于大多数癌症中的多能基质干细胞，在影响 TME 的形成和功能方面发挥着关键作用。据报道，MSCs 通过多种机制支持肿瘤生长，包括（i）分化为其他促肿瘤生成的基质成分，（ii）抑制免疫反应，（iii）促进血管生成，（iv）增强上皮-间充质转化（EMT），（v）富集癌症干细胞样细胞（CSC），（vi）增加肿瘤细胞存活，和（vii）促进肿瘤转移。相反，MSCs 也被报道具有抗肿瘤功能，包括（i）增强免疫反应，（ii）抑制血管生成，（iii）调节细胞信号，和（iv）诱导肿瘤细胞凋亡。尽管有支持这两种观点的文献，但大多数研究表明 MSCs 在 TME 范围内以支持肿瘤的方式发挥作用。当 MSCs 与肿瘤细胞的比例较高时，会观察到肿瘤抑制作用。此外，MSC 的功能似乎依赖于组织类型，并可能依赖于癌症教育来重新编程具有抗肿瘤作用的原始 MSC 为具有抗肿瘤作用的 MSC，从而发展出促肿瘤生成功能。需要进一步的工作来描绘 MSCs 与 TME 其他成分之间的复杂串扰，以准确评估 MSCs 对癌症起始、生长和扩散的影响。
