Sirithammajak Sarawut, Manochantr Sirikul, Tantrawatpan Chairat, Tantikanlayaporn Duangrat, Kheolamai Pakpoom
Center of Excellence in Stem Cell Research and Innovation, Faculty of Medicine, Thammasat University, Pathumthani 12120, Thailand.
Division of Cell Biology, Faculty of Medicine, Thammasat University, Pathumthani 12120, Thailand.
Stem Cells Int. 2022 Nov 11;2022:4020845. doi: 10.1155/2022/4020845. eCollection 2022.
Breast cancer is the most frequently diagnosed malignancy among women, resulting from abnormal proliferation of mammary epithelial cells. The highly vascularized nature of breast tissue leads to a high incidence of breast cancer metastases, resulting in a poor survival rate. Previous studies suggest that human mesenchymal stem cells (hMSCs) play essential roles in the growth, metastasis, and drug responses of many cancers, including breast cancer. However, hMSCs from different sources may release different combinations of cytokines that affect breast cancer differently.
In this study, we have isolated hMSCs from the placenta (PL-hMSCs) and the chorion (CH-hMSCs) and determined how these hMSCs affect the proliferation, migration, invasion, and gene expression of two human breast cancer cells, MCF-7 and MDA-MB-231, as well as the possible mechanisms underlying those effects.
The results showed that the soluble factors derived from PL-hMSCs and CH-hMSCs inhibited the proliferation of MCF-7 and MDA-MB-231 cells but increased the migration of MDA-MB-231 cells. The study of gene expression showed that PL-hMSCs and CH-hMSCs downregulated the expression levels of the protooncogene while upregulating the expression levels of tumor suppressor genes, and in MCF-7 and MDA-MB-231 cells. Furthermore, hMSCs from both sources also increased the expression levels of , and which promote the epithelial-mesenchymal transition and migration of breast cancer cells in both cell lines. The functional study suggests that the suppressive effect of CH-hMSCs and PL-hMSCs on MCF-7 and MDA-MB231 cell proliferation was mediated, at least in part, through IFN-.
Our study suggests that CH-hMSCs and PL-hMSCs inhibited breast cancer cell proliferation by negatively regulating expression and upregulating the expression of the and genes. In contrast, hMSCs from both sources enhanced breast cancer cell migration, possibly by increasing the expression of and genes in those cells.
乳腺癌是女性中最常被诊断出的恶性肿瘤，由乳腺上皮细胞异常增殖引起。乳腺组织的高度血管化特性导致乳腺癌转移的高发生率，从而导致生存率低下。先前的研究表明，人间充质干细胞（hMSCs）在包括乳腺癌在内的许多癌症的生长、转移和药物反应中发挥着重要作用。然而，来自不同来源的hMSCs可能会释放不同组合的细胞因子，对乳腺癌产生不同的影响。
在本研究中，我们从胎盘（PL-hMSCs）和绒毛膜（CH-hMSCs）中分离出hMSCs，并确定这些hMSCs如何影响两种人乳腺癌细胞MCF-7和MDA-MB-231的增殖、迁移、侵袭和基因表达，以及这些影响背后的可能机制。
结果表明，来自PL-hMSCs和CH-hMSCs的可溶性因子抑制了MCF-7和MDA-MB-231细胞的增殖，但增加了MDA-MB-231细胞的迁移。基因表达研究表明，PL-hMSCs和CH-hMSCs下调了原癌基因的表达水平，同时上调了MCF-7和MDA-MB-231细胞中肿瘤抑制基因、和的表达水平。此外，来自这两个来源的hMSCs还增加了、和的表达水平，这促进了两种细胞系中乳腺癌细胞的上皮-间质转化和迁移。功能研究表明，CH-hMSCs和PL-hMSCs对MCF-7和MDA-MB231细胞增殖的抑制作用至少部分是通过IFN-介导的。
我们的研究表明，CH-hMSCs和PL-hMSCs通过负调控表达和上调和基因的表达来抑制乳腺癌细胞增殖。相比之下，来自这两个来源的hMSCs可能通过增加这些细胞中、和基因的表达来增强乳腺癌细胞的迁移。
