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

被引:11
作者
Sun, Yun-Peng [1 ]
Zhang, Ben-Long [2 ]
Duan, Jian-Wen [1 ]
Wu, Huan-Huan [3 ]
Wang, Ben-Quan [1 ]
Yu, Zheng-Ping [1 ]
Yang, Wen-Jun [1 ]
Shan, Yun-Feng [1 ]
Zhou, Meng-Tao [1 ]
Zhang, Qi-Yu [1 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Wenzhou 325015, Zhejiang, Peoples R China
[2] Yiwu Chouzhou Hosp, Dept Gen Surg, Yiwu 322000, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 1, Dept Infect Dis, Wenzhou 325015, Zhejiang, Peoples R China
关键词
NK4; pancreatic cancer; bone marrow-derived mesenchymal stem cells; transduction; HEPATOCYTE GROWTH-FACTOR; TUMOR-GROWTH; C-MET; TARGETED-DELIVERY; INHIBITION; RECEPTOR; ANGIOGENESIS; THERAPY; GENE; MIGRATION;
D O I
10.3390/ijms15033729
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:3729 / 3745
页数:17
相关论文
共 46 条
[11]   Activation of PI3K-Akt-GSK3β pathway mediates hepatocyte growth factor inhibition of RANTES expression in renal tubular epithelial cells [J].
Gong, RJ ;
Rifai, A ;
Dworkin, LD .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 330 (01) :27-33
[12]   Rapid Titration of Measles and Other Viruses: Optimization with Determination of Replication Cycle Length [J].
Grigorov, Boyan ;
Rabilloud, Jessica ;
Lawrence, Philip ;
Gerlier, Denis .
PLOS ONE, 2011, 6 (09)
[13]   The multifaceted roles of glycogen synthase kinase 3β in cellular signaling [J].
Grimes, CA ;
Jope, RS .
PROGRESS IN NEUROBIOLOGY, 2001, 65 (04) :391-426
[14]   Osthole Suppresses Hepatocyte Growth Factor (HGF)-Induced Epithelial-Mesenchymal Transition via Repression of the c-Met/Akt/mTOR Pathway in Human Breast Cancer Cells [J].
Hung, Chao-Ming ;
Kuo, Daih-Huang ;
Chou, Chun-Hung ;
Su, Yen-Chao ;
Ho, Chi-Tang ;
Way, Tzong-Der .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2011, 59 (17) :9683-9690
[15]   Interactions of chemokines and chemokine receptors mediate the migration of mesenchymal stem cells to the impaired site in the brain after hypoglossal nerve injury [J].
Ji, JF ;
He, BP ;
Dheen, ST ;
Tay, SSW .
STEM CELLS, 2004, 22 (03) :415-427
[16]   Molecular biomarkers: their increasing role in the diagnosis, characterization, and therapy guidance in pancreatic cancer [J].
Jimeno, A ;
Hidalgo, M .
MOLECULAR CANCER THERAPEUTICS, 2006, 5 (04) :787-796
[17]   BM cells giving rise to MSC in culture have a heterogeneous CD34 and CD45 phenotype [J].
Kaiser, S. ;
Hackanson, B. ;
Follo, M. ;
Mehlhorn, A. ;
Geiger, K. ;
Ihorst, G. ;
Kapp, U. .
CYTOTHERAPY, 2007, 9 (05) :439-450
[18]   Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells [J].
Kanehira, M. ;
Xin, H. ;
Hoshino, K. ;
Maemondo, M. ;
Mizuguchi, H. ;
Hayakawa, T. ;
Matsumoto, K. ;
Nakamura, T. ;
Nukiwa, T. ;
Saijo, Y. .
CANCER GENE THERAPY, 2007, 14 (11) :894-903
[19]   Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma [J].
Khakoo, Aarif Y. ;
Pati, Shibani ;
Anderson, Stasia A. ;
Reid, William ;
Elshal, Mohamed F. ;
Rovira, Ilsa I. ;
Nguyen, Ahn T. ;
Malide, Daniela ;
Combs, Christian A. ;
Hall, Gentzon ;
Zhang, Jianhu ;
Raffeld, Mark ;
Rogers, Terry B. ;
Stetler-Stevenson, William ;
Frank, Joseph A. ;
Reitz, Marvin ;
Finkel, Toren .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (05) :1235-1247
[20]  
Lai Ren-Xu, 2004, Ai Zheng, V23, P1134