Abstract
GOLPH2 (also called GP73) is a Golgi glycoprotein, which has been identified as a novel tumor marker upregulated in various cancers, including prostate cancer (PCa). GD55 is a novel GOLPH2-regulated oncolytic adenovirus that exhibits a strong killing effect on hepatoma cells. Here, we investigate the antitumor effect of GD55 on prostate cancer stem cell (CSC)-like cells in vitro and in vivo. Prostate CSC-like sphere cells were acquired and enriched by culturing DU145, LNCap or P3 prostate cancer cells in suspension. The prostate CSC-like sphere cells were capable of self-renewal, differentiation and quiescence, displaying tumorigenic feature and chemo-resistance to 5-FU, doxorubicin and DDP. Treatment with GD55 (1, 5, 10 MOI) dose-dependently suppressed the viability of DU145 sphere cells, which was a more pronounced compared to its cytotoxic action on the parental DU145 cells. In a mouse xenograft prostate CSC-like model, intratumoral injection of GD55 markedly suppressed the growth rate of xenograft tumors and induced higher levels of cell death and necrosis within the tumor tissues. Our results demonstrate that GD55 infection exerts strong anticancer effects on prostate CSC-like cells in vitro and in vivo, and has a potential to be used in the clinical therapy of PCa.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Holzbeierlein JM . Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer 2011; 117: 2830–2.
Rajasekhar VK, Studer L, Gerald W, Socci ND, Scher HI . Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-kappaB signalling. Nat Commun 2011; 2: 162.
Magee JA, Piskounova E, Morrison SJ . Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012; 21: 283–96.
Visvader JE, Lindeman GJ . Cancer stem cells: current status and evolving complexities. Cell Stem Cell 2012; 10: 717–28.
Meacham CE, Morrison SJ . Tumour heterogeneity and cancer cell plasticity. Nature 2013; 501: 328–37.
Leong KG, Wang BE, Johnson L, Gao WQ . Generation of a prostate from a single adult stem cell. Nature 2008; 456: 804–8.
Yu DB, Zhong SY, Yang M, Wang YG, Qian QJ, Zheng S, et al. Potent antitumor activity of double-regulated oncolytic adenovirus-mediated ST13 for colorectal cancer. Cancer Sci 2009; 100: 678–83.
Zhang KJ, Wang YG, Cao X, Zhong SY, Wei RC, Wu YM, et al. Potent antitumor effect of interleukin-24 gene in the survivin promoter and retinoblastoma double-regulated oncolytic adenovirus. Hum Gene Ther 2009; 20: 818–30.
Cripe TP, Wang PY, Marcato P, Mahller YY, Lee PW . Targeting cancer-initiating cells with oncolytic viruses. Mol Ther 2009; 17: 1677–82.
Dean M, Fojo T, Bates S . Tumour stem cells and drug resistance. Nat Rev Cancer 2005; 5: 275–84.
Yang Y, Xu H, Huang W, Ding M, Xiao J, Yang D, et al. Targeting lung cancer stem-like cells with TRAIL gene armed oncolytic adenovirus. J Cell Mol Med 2015; 19: 915–23.
Zhao L, Gu J, Dong A, Zhang Y, Zhong L, He L, et al. Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther 2005; 16: 845–58.
Liu XY, Gu JF . Targeting gene-virotherapy of cancer. Cell Res 2006; 16: 740.
Zhang ZL, Zou WG, Luo CX, Li BH, Wang JH, Sun LY, et al. An armed oncolytic adenovirus system, ZD55-gene, demonstrating potent antitumoral efficacy. Cell Res 2003; 13: 481–9.
Zhang Y, Gu J, Zhao L, He L, Qian W, Wang J, et al. Complete elimination of colorectal tumor xenograft by combined manganese superoxide dismutase with tumor necrosis factor-related apoptosis-inducing ligand gene virotherapy. Cancer Res 2006; 66: 4291–8.
Wang Y, Liu T, Huang P, Zhao H, Zhang R, Ma B, et al. A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent antitumor efficacy in hepatocellular carcinoma. Oncotarget 2015; 6: 13564–78.
Zhang X, Meng S, Zhang R, Ma B, Liu T, Yang Y, et al. GP73-regulated oncolytic adenoviruses possess potent killing effect on human liver cancer stem-like cells. Oncotarget 2016; 7: 29346–58.
Yang Y, Xu H, Shen J, Wu S, Xiao J, Xu Y, et al. RGD-modifided oncolytic adenovirus exhibited potent cytotoxic effect on CAR-negative bladder cancer-initiating cells. Cell Death Dis 2015; 14: 128.
Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ . Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res 2005; 65: 10946–51.
Collura A, Marisa L, Trojan D, Buhard O, Lagrange A, Saget A, et al. Extensive characterization of sphere models established from colorectal cancer cell lines. Cell Mol Life Sci 2013; 70: 729–42.
Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63: 5821–8.
Ding BS, James D, Iyer R, Falciatori I, Hambardzumyan D, Wang S, et al. Prominin 1/CD133 endothelium sustains growth of proneural glioma. PLoS One 2013; 8: 1093–7.
Missol-Kolka E, Karbanova J, Janich P, Haase M, Fargeas CA, Huttner WB, et al. Prominin-1 (CD133) is not restricted to stem cells located in the basal compartment of murine and human prostate. Prostate 2011; 71: 254–67.
Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL . CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer 2008; 98: 756–65.
Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene 2006; 25: 1696–708.
Wang L, Huang X, Zheng X, Wang X, Li S, Zhang L, et al. Enrichment of prostate cancer stem-like cells from human prostate cancer cell lines by culture in serum-free medium and chemoradiotherapy. Int J Biol Sci 2013; 9: 472–9.
Gu G, Yuan J, Wills M, Kasper S . Prostate cancer cells with stem cell characteristics reconstitute the original human tumor in vivo. Cancer Res 2007; 67: 4807–15.
Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C, et al. Functional evidence that the self-renewal gene NANOG regulates human tumor development. Stem Cells 2009; 27: 993–1005.
Jeter CR, Liu B, Liu X, Chen X, Liu C, Calhoun-Davis T, et al. NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene 2011; 30: 3833–45.
Ugolkov AV, Eisengart LJ, Luan C, Yang XJ . Expression analysis of putative stem cell markers in human benign and malignant prostate. Prostate 2011; 71: 18–25.
Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A 2009; 106: 268–73.
Thaci B, Ulasov IV, Ahmed AU, Ferguson SD, Han Y, Lesniak MS . Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation. Gene Ther 2013; 20: 318–27.
Liu XY . The excellent anti-tumour strategy (CTGVT, OV-gene) and the excellent anti-tumor gene (IL-24). Int J Biomed Sci 2012; 8: 87–93.
Chen LG, Wang HJ, Yao HB, Guan TP, Wu F, He XJ, et al. GP73 is down-regulated in gastric cancer and associated with tumor differentiation. World J Surg Oncol 2013; 11: 132.
Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, Reinhardt F, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 2013; 154: 61–74.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (No 81272687 and 81573000), Zhejiang Provincial Natural Science Foundation of China (No LY16H160056), Zhejiang Province Health Department (No 2014RCA022), Grant for 521 Talent Project of ZSTU and Academician Workstation of Zhejiang Province.
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary information is available at the website of Acta Pharmacologica Sinica.
Supplementary information
Supplementary Information
Supplementary Figure S1–S3 (DOC 447 kb)
Rights and permissions
About this article
Cite this article
Ying, C., Xiao, Bd., Qin, Y. et al. GOLPH2-regulated oncolytic adenovirus, GD55, exerts strong killing effect on human prostate cancer stem-like cells in vitro and in vivo. Acta Pharmacol Sin 39, 405–414 (2018). https://doi.org/10.1038/aps.2017.91
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/aps.2017.91
Keywords
This article is cited by
-
Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer
Scientific Reports (2024)
-
The role of oncolytic virotherapy and viral oncogenes in the cancer stem cells: a review of virus in cancer stem cells
Cancer Cell International (2023)
-
Oncolytic virotherapy: basic principles, recent advances and future directions
Signal Transduction and Targeted Therapy (2023)
-
MPZL1 suppresses the cancer stem-like properties of lung cancer through β-catenin/TCF4 signaling
Functional & Integrative Genomics (2023)
-
Intratumoral delivery of a Tim-3 antibody-encoding oncolytic adenovirus engages an effective antitumor immune response in liver cancer
Journal of Cancer Research and Clinical Oncology (2023)
