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Effect of NK4 Transduction in Bone Marrow-Derived Mesenchymal Stem Cells on Biological Characteristics of Pancreatic Cancer Cells

机译:骨髓间充质干细胞中NK4转导对胰腺癌细胞生物学特性的影响

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摘要

Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF) which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs) strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer.
机译:胰腺癌的预后通常较差,并且尚未开发出可有效治疗胰腺癌的基因疗法。由于骨髓源间充质干细胞(MSCs)的独特特征是它们迁移到肿瘤组织,因此我们想确定MSCs是否可以作为针对胰腺癌的基因治疗手段。首先,我们成功地从SD大鼠中提取了MSC。接下来,通过腺病毒载体用NK4有效地转导MSC,NK4是肝细胞生长因子(HGF)的拮抗剂,其包括HGF的N末端和随后的四个kringle结构域。然后,我们证实大鼠MSC优先迁移到胰腺癌细胞。最后,在共培养后,表达NK4的MSC(NK4-MSC)强烈抑制胰腺癌细胞SW1990的增殖和迁移。这些结果表明,MSCs可以作为针对胰腺癌的基因治疗的载体。

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