MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors.
MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors.
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作者：
基质金属蛋白酶（MMP）是已知在细胞迁移中起作用的蛋白酶家族。在本研究中，我们评估了MMP-2在人髓母细胞瘤肿瘤模型中对人脐带血来源的干细胞（hUCBSC）向性的作用。MMP-2抑制干细胞向髓母细胞瘤的嗜性的后果进行了研究，通过使用细胞培养插入，transwell室测定，MMP-2和迁移分子的蛋白质印迹，和免疫组化的干细胞迁移。与来自模拟和乱序载体（Ad-SV）感染的细胞的条件培养基相比，来自用编码MMP-2 siRNA的腺病毒载体（Ad-MMP-2 si）感染的Daoy/D283细胞的条件培养基减少干细胞迁移。此外，肿瘤细胞中的MMP-2抑制降低了肿瘤条件培养基中SDF 1的表达，这导致SDF 1/CXCR 4信号传导受损，导致干细胞对肿瘤细胞的向性降低。我们进一步表明，MMP-2抑制肿瘤细胞抑制干细胞对髓母细胞瘤肿瘤在体内的嗜性。总之，我们的结论是，hUCBSCs可以整合到人髓母细胞瘤后，局部交付和MMP-2的肿瘤细胞表达介导的这种反应通过SDF 1/CXCR 4轴。
Matrix metalloproteinases (MMPs) are a family of proteinases known to play a role in cell migration. In the present study, we evaluated the role of MMP-2 on tropism of human cord blood derived stem cells (hUCBSCs) in a human medulloblastoma tumor model. Consequences of MMP-2 inhibition on stem cell tropism towards medulloblastoma were studied in terms of stem cell migration by using cell culture inserts, transwell chamber assay, western blotting for MMP-2 and migratory molecules, and immunohistochemistry. Conditioned medium from Daoy/D283 cells infected with adenoviral vector encoding MMP-2 siRNA (Ad-MMP-2 si) reduced stem cell migration as compared to conditioned medium from mock and scrambled vector (Ad-SV) infected cells. In addition, MMP-2 inhibition in the tumor cells decreased the expression of SDF1 in the tumor conditioned medium, which results in impaired SDF1/CXCR4 signaling leading to decreased stem cell tropism towards the tumor cells. We further show that MMP-2 inhibition in the tumor cells repressed stem cell tropism towards medulloblastoma tumors in vivo. In summary, we conclude that hUCBSCs can integrate into human medulloblastoma after local delivery and that MMP-2 expression by the tumor cells mediates this response through the SDF1/CXCR4 axis.
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影响因子：
11.5
作者：
Özen, Ö;Krebs, B;Herms, J
通讯作者：
Herms, J
影响因子：
3.3
作者：
Reiss, K;Mentlein, R;Hartmann, D
通讯作者：
Hartmann, D
影响因子：
10.1
作者：
De Becker, Ann;Van Hummelen, Paul;Van Riet, Ivan
通讯作者：
Van Riet, Ivan
DOI：
10.1073/pnas.2235846100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Rubin, JB;Kung, AL;Segal, RA
通讯作者：
Segal, RA
影响因子：
5.2
作者：
Guo, Y;Hangoc, G;Broxmeyer, HE
通讯作者：
Broxmeyer, HE