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http://dx.doi.org/10.4062/biomolther.2013.112

Vesicular Stomatitis Virus G Glycoprotein and ATRA Enhanced Bystander Killing of Chemoresistant Leukemic Cells by Herpes Simplex Virus Thymidine Kinase/Ganciclovir  

Hu, Chenxi (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
Chen, Zheng (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
Zhao, Wenjun (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
Wei, Lirong (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
Zheng, Yanwen (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
He, Chao (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
Zeng, Yan (Department of Pharmacology, University of Minnesota)
Yin, Bin (Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University)
Publication Information
Biomolecules & Therapeutics / v.22, no.2, 2014 , pp. 114-121 More about this Journal
Abstract
Refractoriness of acute myeloid leukemia (AML) cells to chemotherapeutics represents a major clinical barrier. Suicide gene therapy for cancer has been attractive but with limited clinical efficacy. In this study, we investigated the potential application of herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) based system to inhibit chemoresistant AML cells. We first generated Ara-C resistant K562 cells and doxorubicin-resistant THP-1 cells. We found that the HSV-TK/GCV anticancer system suppressed drug resistant leukemic cells in culture. Chemoresistant AML cell lines displayed similar sensitivity to HSV-TK/GCV. Moreover, HSV-TK/GCV killing of leukemic cells was augmented to a mild but significant extent by all-trans retinoic acid (ATRA) with concomitant upregulation of Connexin 43, a major component of gap junctions. Interestingly, HSV-TK/GCV killing was enhanced by expression of vesicular stomatitis virus G glycoprotein (VSV-G), a fusogenic membrane protein, which also increased leukemic cell fusion. Co-culture resistant cells expressing HSV-TK and cells stably transduced with VSV-G showed that expression of VSV-G could promote the bystander killing effect of HSV-TK/GCV. Furthermore, combination of HSV-TK/GCV with VSV-G plus ATRA produced more pronounced antileukemia effect. These results suggest that the HSV-TK/GCV system in combination with fusogenic membrane proteins and/or ATRA could provide a strategy to mitigate the chemoresistance of AML.
Keywords
VSV-G; ATRA; Bystander killing; Chemoresisitant leukemia cells; HSV-TK/GCV;
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1 Yang, J., Liu, T. J., Jiang, Y. X. and Lu, Y. (2012) ATRA enhances the bystander effect of suicide gene therapy driven by the specific promoter LEP 503 in human lens epithelial cells. Mol. Vis. 18, 2053-2066.
2 Zhu, D., Lam, D. H., Purwanti, Y. I., Goh, S. L., Wu, C., Zeng, J., Fan, W. and Wang, S. (2013) Systemic delivery of fusogenic membrane glycoprotein-expressing neural stem cells to selectively kill tumor cells. Mol. Ther. 21, 1621-1630.   DOI
3 Pulte, D., Gondos, A. and Brenner, H. (2010) Expected long-term survival of patients diagnosed with acute myeloblastic leukemia during 2006-2010. Ann. Oncol. 21, 335-341.   DOI
4 Park, J. Y., Elshami, A. A., Amin, K., Rizk, N., Kaiser, L. R. and Albelda, S. M. (1997) Retinoids augment the bystander effect in vitro and in vivo in herpes simplex virus thymidine kinase/ganciclovir-mediated gene therapy. Gene Ther. 4, 909-917.   DOI
5 Robe, P. A., Jolois, O., N'Guyen, M., Princen, F., Malgrange, B., Merville, M. P. and Bours, V. (2004) Modulation ofthe HSV-TK/ganciclovir bystander effect by n-butyrate in glioblasto-ma: correlation with gap-junction intercellular communication. Int. J. Oncol. 25, 187-192.
6 Takenaga, K., Tagawa, M. and Sakiyama, S. (1996) Therapeutic potency of transduction with herpes simplex virus thymidine kinase gene against multidrug resistant mouse leukemia cells. Anticancer Res. 16, 681-685.
7 Tanaka, T., Yamasaki, H. and Mesnil, M. (2001) Stimulation of intercellular communication of poor-communicating cells by gap-junction-competent cells enhances the HSV-TK/GCV bystander effect in vitro. Int. J. Cancer 91, 538-542.   DOI
8 Van Dillen, I. J., Mulder, N. H., Vaalburg, W., de Vries, E. F. and Hospers, G. A. (2002) Influence of the bystander effect on HSV-tk/GCV gene therapy. A review. Curr. Gene Ther. 2, 307-322.   DOI
9 Yin, B., Kogan, S. C., Dickins, R. A., Lowe, S. W. and Largaespada, D. A. (2006a) Trp53 loss during in vitro selection contributes to acquired Ara-C resistance in acute myeloid leukemia. Exp. Hematol. 34, 631-641.   DOI
10 Yin, B., Morgan, K., Hasz, D. E., Mao, Z. and Largaespada, D. A. (2006b) Nfl gene inactivation in acute myeloid leukemia cells confers cytarabine resistance through MAPK and mTOR pathways. Leukemia 20, 151-154.   DOI
11 Hoggarth, J. H., Jones, E., Ensser, A. and Meredith, D. M. (2004) Functional expression of thymidine kinase in human leukaemic and colorectal cells, delivered as EGFP fusion protein by herpesvirus saimiri-based vector. Cancer Gene Ther. 11, 613-624.   DOI
12 Namba, H., Iwadate, Y., Kawamura, K., Sakiyama, S. and Tagawa, M. (2001) Efficacy of the bystander effect in the herpes simplex virus thymidine kinase-mediated gene therapy is influenced by the expression of connexin43 in the target cells. Cancer Gene Ther. 8, 414-420.   DOI   ScienceOn
13 Onodera, M. (2008) Gene and cell therapy for relapsed leukemia after allo-stem cell transplantation. Front. Biosci. 13, 3408-3414.
14 Garg, H. and Blumenthal, R. (2008) Role of HIV Gp41 mediated fusion/hemifusion in bystander apoptosis. Cell. Mol. Life. Sci. 65, 3134-3144.   DOI
15 Hoffmann, D., Grunwald, T., Kuate, S. and Wildner, O. (2007) Mechanistic analysis and comparison of viral fusogenic membrane proteins for their synergistic effects onchemotherapy. Cancer Biol. Ther. 6, 510-518.   DOI
16 Kawamura, K., Bahar, R., Namba, H., Seimiya, M., Takenaga, K., Hamada, H., Sakiyama, S. and Tagawa, M. (2001) Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication. Int. J. Oncol. 18, 117-120.
17 Li, S., Gao, Y., Pu, K., Ma, L., Song, X. and Liu, Y. (2011) All-trans retinoic acid enhances bystander effect of suicide-gene therapy against medulloblastomas. Neurosci. Lett. 503, 115-119.   DOI
18 Miyake, K., Inokuchi, K., Miyake, N., Dan, K. and Shimada, T. (2007) HIV vector-mediated targeted suicide gene therapy for adult T-cell leukemia. Gene Ther. 14, 1662-1667.   DOI
19 Matono, S., Tanaka, T., Sueyoshi, S., Yamana, H., Fujita, H. and Shirouzu, K. (2003) Bystander effect in suicide gene therapy is directly proportional to the degree of gap junctional intercellular communication in esophageal cancer. Int. J. Oncol. 23, 1309-1315.
20 Mesnil, M. and Yamasaki, H. (2000) Bystander effect in herpes simplex virus-thymidine kinase/ganciclovir cancer gene therapy: role of gap-junctional intercellular communication. Cancer Res. 60, 3989-3999.
21 Neschadim, A., Wang, J. C., Lavie, A. and Medin, J. A. (2012) Bystander killing of malignant cells via the delivery of engineered thymidine-active deoxycytidine kinase for suicide gene therapy of cancer. Cancer Gene Ther. 19, 320-327.   DOI
22 Grignet-Debrus, C., Cool, V., Baudson, N., Velu, T. and Calberg-Bacq, C. M. (2000) The role of cellular- and prodrug-associated factors in the bystander effect induced by the Varicella zoster and Herpes simplex viral thymidine kinases in suicide gene therapy. Cancer Gene Ther. 7, 1456-1468.   DOI
23 Galanis, E., Bateman, A., Johnson, K., Diaz, R. M., James, C. D., Vile, R. and Russell, S. J. (2001) Use of viral fusogenic membrane glycoproteins as novel therapeutic transgenes in gliomas. Hum. Gene Ther. 12, 811-821.   DOI
24 Borchers, S., Provasi, E., Silvani, A., Radrizzani, M., Benati, C., Dammann, E., Krons, A., Kontsendorn, J., Schmidtke, J., Kuehnau, W., von Neuhoff , N., Stadler, M., Ciceri, F., Bonini, C., Ganser, A., Hertenstein, B. and Weissinger, E. M. (2011) Genetically modified donor leukocyte transfusion and graft-versus-leukemia effect after allogeneic stem cell transplantation. Hum. Gene Ther. 22, 829-841.   DOI
25 Drake, R. R., Pitlyk, K., McMasters, R. A., Mercer, K. E., Young, H. and Moyer, M. P. (2000) Connexin-independent ganciclovir-mediated killing conferred on bystander effect-resistant cell lines by a herpes simplex virus-thymidine kinase-expressing colon cell line. Mol. Ther. 2, 515-523.   DOI
26 Casucci, M., Perna, S. K., Falcone, L , Camisa, B., Magnani, Z., Bernardi, M., Crotta, A., Tresoldi, C., Fleischhauer, K., Ponzoni, M., Gregori, S., Caligaris Cappio, F., Ciceri, F., Bordignon, C., Cignetti, A., Bondanza, A. and Bonini, C. (2013) Graft-versus-leukemia effect of HLA-haploidentical central-memory T-cells expanded with leukemic APCs and modified with a suicide gene. Mol. Ther. 21, 466-475.   DOI
27 Chhipa, R. R. and Bhat, M. K. (2007) Bystander killing of breast cancer MCF-7 cells by MDA-MB-231 cells exposed to 5-fluorouracil is mediated via Fas. J. Cell. Biochem. 101, 68-79.   DOI
28 Chen, W., Yan, C., Hou, J., Pu, J., Ouyang, J. and Wen, D. (2008) ATRA enhances bystander effect of suicide gene therapy in the treatment of prostate cancer. Urol. Oncol. 26, 397-405.   DOI
29 Dachs, G. U., Hunt, M. A., Syddall, S., Singleton, D. C. and Patterson, A. V. (2009) Bystander or no bystander for gene directed enzyme prodrug therapy. Molecules 14, 4517-4545.   DOI   ScienceOn
30 Duarte, S., Carle, G., Faneca, H., de Lima, M. C. and Pierrefite-Carle, V. (2012) Suicide gene therapy in cancer: where do we stand now? Cancer Lett. 324, 160-170.   DOI
31 Dilber, M. S. and Gahrton, G. (2001) Suicide gene therapy: possible applications in haematopoietic disorders. J. Intern. Med. 249, 359-367.   DOI
32 Bondanza, A., Hambach, L., Aghai, Z., Nijmeijer, B., Kaneko, S., Mastaglio, S., Radrizzani, M., Fleischhauer, K., Ciceri, F., Bordignon, C., Bonini, C. and Goulmy, E. (2011) IL-7 receptor expression identifies suicide gene-modified allospecific CD8+ T cells capable of self-renewal and differentiation into antileukemia effectors. Blood 117, 6469-6478.   DOI   ScienceOn
33 Asklund, T., Appelskog, I. B., Ammerpohl, O., Langmoen, I. A., Dilber, M. S., Aints, A., Ekstrom, T. J. and Almqvist, P. M. (2003) Gap junction-mediated bystander effect in primary cultures of human malignant gliomas with recombinant expression of the HSVtk gene. Exp. Cell Res. 284, 185-195.
34 Aiuti, A., Biasco, L., Scaramuzza, S., Ferrua, F., Cicalese, M. P., Baricordi, C., Dionisio, F., Calabria, A., Giannelli, S., Castiello, M. C., Bosticardo, M., Evangelio, C., Assanelli, A.,Casiraghi, M., Di Nunzio, S., Callegaro, L., Benati, C., Rizzardi, P., Pellin, D., Di Serio, C., Schmidt, M., Von Kalle, C., Gardner, J., Mehta, N., Neduva, V., Dow, D. J., Galy, A., Miniero, R., Finocchi, A., Metin, A., Banerjee, P. P., Orange, J. S., Galimberti, S., Valsecchi, M. G., Biffi, A., Montini, E., Villa, A., Ciceri, F., Roncarolo, M. G. and Naldini, L. (2013) Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 341, 1233151.   DOI
35 Braun, S. E., Chen, K., Battiwalla, M. and Cornetta, K. (1997) Gene therapy strategies for leukemia. Mol. Med. Today 3, 39-46.   DOI
36 Blumenthal, M., Skelton, D., Pepper, K. A., Jahn, T., Methangkool, E. and Kohn, D. B. (2007) Effective suicide gene therapy for leukemia in a model of insertional oncogenesis in mice. Mol. Ther. 15, 183-192.   DOI
37 Yin, B., Delwel, R., Valk, P. J., Wallace, M. R., Loh, M. L., Shannon, K. M. and Largaespada, D. A. (2009) A retroviral mutagenesis screen reveals strong cooperation between Bcl11a overexpression and loss of the Nf1 tumor suppressor gene. Blood 113, 1075-1085.
38 Biffi, A., Montini, E., Lorioli, L., Cesani, M., Fumagalli, F., Plati, T., Baldoli, C., Martino, S., Calabria, A., Canale, S., Benedicenti, F., Vallanti, G., Biasco, L., Leo, S., Kabbara, N., Zanetti, G., Rizzo, W. B., Mehta, N. A., Cicalese, M. P., Casiraghi, M., Boelens, J. J., Del Carro, U., Dow, D. J., Schmidt, M., Assanelli, A., Neduva, V., Di Serio, C., Stupka, E., Gardner, J., von Kalle, C., Bordignon, C., Ciceri, F., Rovelli, A., Roncarolo, M. G., Aiuti, A., Sessa, M. and Naldini, L. (2013) Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341, 1233158.   DOI