Graduate School of Biotechnology, Kyung Hee University, Yongin, Korea.
Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea.
FEBS Open Bio. 2024 Jul;14(7):1192-1204. doi: 10.1002/2211-5463.13815. Epub 2024 May 8.
Glioblastoma recruits various nontransformed cells from distant tissues. Although bone marrow-derived mesenchymal stem cells (MSCs) have been observed migrating to glioblastoma, the underlying mechanism driving MSC migration toward glioblastoma remains unclear. Tumor vascularity is critical in the context of recurrent glioblastoma and is closely linked to the expression of stromal cell-derived factor-1 (SDF-1). We demonstrated that cadherin-6 mediated MSC migration both toward SDF-1 and toward glioblastoma cells. Cadherin-6 knockdown resulted in the downregulation of MSCs capacity to migrate in response to SDF-1. Furthermore, MSCs with cadherin-6 knockdown exhibited impaired migration in response to conditioned media derived from glioblastoma cell lines (U87 and U373) expressing SDF-1, thus simulating the glioblastoma microenvironment. Moreover, MSCs enhanced the vasculogenic capacity of U87 cells without increasing the proliferation, cancer stem cell characteristics, or migration of U87. These results suggest that the current strategy of utilizing MSCs as carriers for antiglioblastoma drugs requires careful examination. Furthermore, cadherin-6 may represent a novel potential target for controlling the recruitment of MSCs toward glioblastoma.
胶质母细胞瘤从远处组织招募各种非转化细胞。尽管已经观察到骨髓来源的间充质干细胞（MSCs）迁移到胶质母细胞瘤，但驱动 MSC 向胶质母细胞瘤迁移的潜在机制仍不清楚。肿瘤血管生成在复发性胶质母细胞瘤中至关重要，并且与基质细胞衍生因子-1（SDF-1）的表达密切相关。我们证明了钙黏蛋白-6介导的 MSC 向 SDF-1 和胶质母细胞瘤细胞的迁移。钙黏蛋白-6 敲低导致 MSC 对 SDF-1 迁移的能力下调。此外，钙黏蛋白-6 敲低的 MSC 在对表达 SDF-1 的胶质母细胞瘤细胞系（U87 和 U373）的条件培养基的反应中表现出迁移受损，从而模拟了胶质母细胞瘤微环境。此外，MSCs 增强了 U87 细胞的血管生成能力，而不会增加 U87 的增殖、癌症干细胞特征或迁移。这些结果表明，目前利用 MSCs 作为抗胶质母细胞瘤药物载体的策略需要仔细考虑。此外，钙黏蛋白-6 可能代表控制 MSC 向胶质母细胞瘤募集的一个新的潜在靶点。
