Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, No. 109 Xueyuan Xi Road, Wenzhou, 325027, Zhejiang, China.
Apoptosis. 2022 Dec;27(11-12):840-851. doi: 10.1007/s10495-022-01749-6. Epub 2022 Jul 18.
In the last decade, there has been a rapid expansion in tumor targeted therapy using mesenchymal stem cells (MSCs) based on their unique tropism towards cancer cells. Despite similarities in morphology, immunophenotype, and differential potent in vitro, MSCs originated from different tissues do not necessarily have equivalent biological behaviors. It is important to screen the most chemotactic MSCs to cancer cells. In this study, different MSCs were isolated from various human tissues including adipose, umbilical cord, amniotic membrane, and chorion. The chemotaxis of human MSCs to cervical cancer cells was measured by CCK-8, ELISA and Transwell invasion assays. Western blotting was performed to explore the underlying mechanisms. MSCs derived from distinct sources can be differently recruited to cervical cancer cells, among which chorion-derived MSC (CD-MSC) possessed the strongest tropic capacity. CXCL12 was found to be highly secreted by cervical cancer cells, in parallel with the expression of CXCR4 in all MSCs. CD-MSC displayed the highest level of CXCR4. These results indicated that CXCL12/CXCR4 pathway contributed to the different chemotaxis to cervical cancer cells of each MSCs. This study proposed that CD-MSC with the highest CXCR4 expression is a promising therapeutic vehicle for targeted therapy in cervical cancer.
在过去的十年中，基于间充质干细胞（MSCs）对癌细胞的独特趋向性，肿瘤靶向治疗得到了快速发展。尽管 MSCs 在形态、免疫表型和体外分化潜能上具有相似性，但来源于不同组织的 MSCs 并不一定具有等效的生物学行为。筛选对癌细胞具有最强趋化性的 MSC 非常重要。在这项研究中，我们从不同的人体组织（包括脂肪、脐带、羊膜和绒毛膜）中分离出不同的 MSCs。通过 CCK-8、ELISA 和 Transwell 侵袭实验测量人 MSCs 向宫颈癌细胞的趋化性。通过 Western blot 探索潜在机制。不同来源的 MSCs 可以被不同程度地招募到宫颈癌细胞中，其中绒毛膜来源的 MSC（CD-MSC）具有最强的趋化能力。研究发现，宫颈癌细胞高度分泌 CXCL12，同时所有 MSCs 中均表达 CXCR4。CD-MSC 显示出最高水平的 CXCR4。这些结果表明，CXCL12/CXCR4 途径有助于每种 MSC 对宫颈癌细胞的不同趋化性。本研究提出，具有最高 CXCR4 表达的 CD-MSC 是宫颈癌靶向治疗的一种很有前途的治疗载体。
