DOI QR코드

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Survival Association and Cell Cycle Effects of B7H3 in Neuroblastoma

  • Zhang, Haibo (Department of Neurosurgery, Huashan Hospital, Fudan University) ;
  • Zhang, Jinsen (Department of Neurosurgery, Huashan Hospital, Fudan University) ;
  • Li, Chunjie (Institutes of Biomedical Sciences, Fudan University) ;
  • Xu, Hao (Department of Neurosurgery, Huashan Hospital, Fudan University) ;
  • Dong, Rui (Department of Pediatric Surgery, Children's Hospital of Fudan University) ;
  • Chen, Clark C. (Department of Neurosurgery, University of Minnesota) ;
  • Hua, Wei (Department of Neurosurgery, Huashan Hospital, Fudan University)
  • 투고 : 2019.12.12
  • 심사 : 2020.03.11
  • 발행 : 2020.11.01

초록

Objective : The function of B7H3, a member of the B7 family of proteins, in neuroblastoma (NB) remains poorly characterized. Here we examine the expression pattern of B7H3 in clinical NB specimens and characterize the phenotype of B7H3 knock-down in NB cell line. Methods : Immunohistochemical (IHC) staining was carried out to assess the expression of B7H3 in clinical NB specimens. Survival association was analyzed using five Gene Expression Omnibus (GEO) datasets (GSE85047, GSE45480, GSE62564, GSE16476, GSE49710). Clonogenic survival and flow cytometry were performed after B7H3 knockdown to assess the cellular proliferation and cell survival in vitro. Impact of B7H3 silencing on NB growth was examined in vivo using the SH-SY5Y xenograft model. Results : On IHC staining, B7H3 was widely expressed in clinical NB specimens. Analysis of the transcriptional profiles of five GEO datasets clinically annotated NB specimens revealed that decreased B7H3 expression was associated with improved overall survival. B7H3 knockdown suppressed the proliferation of the SH-SY5Y NB model in vitro and in vivo. Cell cycle analysis revealed that B7H3 silencing induced G1/S arrest. This arrest was associated with the suppression of E2F1 expression and induction of Rb expression. Conclusion : Our results demonstrate that B7H3 expression correlate with clinical survival in NB patients. Preliminary studies suggest that B7H3 may mediate the G1/S transition.

키워드

참고문헌

  1. Bertoli C, Skotheim JM, de Bruin RA : Control of cell cycle transcription during G1 and S phases. Nat Rev Mol Cell Biol 14 : 518-528, 2013 https://doi.org/10.1038/nrm3629
  2. Castriconi R, Dondero A, Augugliaro R, Cantoni C, Carnemolla B, Sementa AR, et al. : Identification of 4Ig-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci U S A 101 : 12640-12645, 2004 https://doi.org/10.1073/pnas.0405025101
  3. Dong P, Xiong Y, Yue J, Hanley SJB, Watari H : B7H3 as a promoter of metastasis and promising therapeutic target. Front Oncol 8 : 264, 2018 https://doi.org/10.3389/fonc.2018.00264
  4. Du H, Hirabayashi K, Ahn S, Kren NP, Montgomery SA, Wang X, et al. : Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells. Cancer Cell 35 : 221-237.e8, 2019 https://doi.org/10.1016/j.ccell.2019.01.002
  5. Eleveld TF, Oldridge DA, Bernard V, Koster J, Colmet Daage L, Diskin SJ, et al. : Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat Genet 47 : 864-871, 2015 https://doi.org/10.1038/ng.3333
  6. Jeon H, Vigdorovich V, Garrett-Thomson SC, Janakiram M, Ramagopal UA, Abadi YM, et al. : Structure and cancer immunotherapy of the B7 family member B7x. Cell Rep 9 : 1089-1098, 2014 https://doi.org/10.1016/j.celrep.2014.09.053
  7. John RR, Malathi N, Ravindran C, Anandan S : Mini review: multifaceted role played by cyclin D1 in tumor behavior. Indian J Dent Res 28 : 187-192, 2017 https://doi.org/10.4103/ijdr.IJDR_697_16
  8. Lim S, Liu H, Madeira da Silva L, Arora R, Liu Z, Phillips JB, et al. : Immunoregulatory protein B7-H3 reprograms glucose metabolism in cancer cells by ROS-mediated stabilization of $HIF1{\alpha}$. Cancer Res 76 : 2231-2242, 2016 https://doi.org/10.1158/0008-5472.CAN-15-1538
  9. Liu H, Tekle C, Chen YW, Kristian A, Zhao Y, Zhou M, et al. : B7-H3 silencing increases paclitaxel sensitivity by abrogating Jak2/Stat3 phosphorylation. Mol Cancer Ther 10 : 960-971, 2011 https://doi.org/10.1158/1535-7163.MCT-11-0072
  10. Luo D, Xiao H, Dong J, Li Y, Feng G, Cui M, et al. : B7-H3 regulates lipid metabolism of lung cancer through SREBP1-mediated expression of FASN. Biochem Biophys Res Commun 482 : 1246-1251, 2017 https://doi.org/10.1016/j.bbrc.2016.12.021
  11. Maris JM : Recent advances in neuroblastoma. N Engl J Med 362 : 2202-2211, 2010 https://doi.org/10.1056/NEJMra0804577
  12. McNair C, Xu K, Mandigo AC, Benelli M, Leiby B, Rodrigues D, et al. : Differential impact of RB status on E2F1 reprogramming in human cancer. J Clin Invest 128 : 341-358, 2018 https://doi.org/10.1172/jci93566
  13. Otto T, Sicinski P : Cell cycle proteins as promising targets in cancer therapy. Nat Rev Cancer 17 : 93-115, 2017 https://doi.org/10.1038/nrc.2016.138
  14. Peifer M, Hertwig F, Roels F, Dreidax D, Gartlgruber M, Menon R, et al. : Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature 526 : 700-704, 2015 https://doi.org/10.1038/nature14980
  15. Seaman S, Zhu Z, Saha S, Zhang XM, Yang MY, Hilton MB, et al. : Eradication of tumors through simultaneous ablation of CD276/B7-H3-positive tumor cells and tumor vasculature. Cancer Cell 31 : 501-515. e8, 2017 https://doi.org/10.1016/j.ccell.2017.03.005
  16. Tan WQ, Chen G, Ye M, Jia B : Artemether regulates chemosensitivity to doxorubicin via regulation of B7-H3 in human neuroblastoma cells. Med Sci Monit 23 : 4252-4259, 2017 https://doi.org/10.12659/MSM.902068
  17. Tekle C, Nygren MK, Chen YW, Dybsjord I, Nesland JM, Maelandsmo GM, et al. : B7-H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasis-associated genes. Int J Cancer 130 : 2282-2290, 2012 https://doi.org/10.1002/ijc.26238
  18. Wu J, Wang F, Liu X, Zhang T, Liu F, Ge X, et al. : Correlation of IDH1 and B7H3 expression with prognosis of CRC patients. Eur J Surg Oncol 44 : 1254-1260, 2018 https://doi.org/10.1016/j.ejso.2018.05.005
  19. Yuan H, Wei X, Zhang G, Li C, Zhang X, Hou J : B7-H3 over expression in prostate cancer promotes tumor cell progression. J Urol 186 : 1093-1099, 2011 https://doi.org/10.1016/j.juro.2011.04.103
  20. Zhang J, Wang J, Marzese DM, Wang X, Yang Z, Li C, et al. : B7H3 regulates differentiation and serves as a potential biomarker and theranostic target for human glioblastoma. Lab Invest 99 : 1117-1129, 2019 https://doi.org/10.1038/s41374-019-0238-5
  21. Zhang T, Jiang B, Zou ST, Liu F, Hua D : Overexpression of B7-H3 augments anti-apoptosis of colorectal cancer cells by Jak2-STAT3. World J Gastroenterol 21 : 1804-1813, 2015 https://doi.org/10.3748/wjg.v21.i6.1804

피인용 문헌

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  2. Gene clusters based on OLIG2 and CD276 could distinguish molecular profiling in glioblastoma vol.19, pp.1, 2020, https://doi.org/10.1186/s12967-021-03083-y