Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Source:
      Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: Dordrecht, Boston, Reidel.
    • Subject Terms:
    • Abstract:
      Background: Cervical cancer is a common gynecologic malignant tumor, but the critical factors affecting cervical cancer progression are still not well demonstrated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been widely recognized as an anti-inflammatory factor to regulate macrophage polarization. In this study, the effect and mechanism of MANF on cervical cancer were preliminarily explored.
      Methods and Results: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo.
      Conclusion: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment.
      (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
    • References:
      Cohen PA, Jhingran A, Oaknin A, Denny L (2019) Cervical cancer. Lancet 393:169–182. (PMID: 3063858210.1016/S0140-6736(18)32470-X)
      Zhang L, Wang X, Lai M (2015) Modulation of epithelial-to-mesenchymal cancerous transition by natural products. Fitoterapia 106:247–255. (PMID: 2638638910.1016/j.fitote.2015.09.013)
      Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139:871–890. (PMID: 1994537610.1016/j.cell.2009.11.007)
      Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715. (PMID: 18485877272803210.1016/j.cell.2008.03.027)
      Singh A, Settleman J (2010) EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29:4741–4751. (PMID: 20531305317671810.1038/onc.2010.215)
      Shibue T, Weinberg RA (2017) EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Nat Rev Clin Oncol 14:611–629. (PMID: 28397828572036610.1038/nrclinonc.2017.44)
      Lambert AW, Pattabiraman DR, Weinberg RA (2017) Emerging biological principles of metastasis. Cell 168:670–691. (PMID: 28187288530846510.1016/j.cell.2016.11.037)
      Rojas-Puentes L, Cardona AF, Carranza H, Vargas C, Jaramillo LF, Zea D et al (2016) Epithelial-mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy. Cancer Med 5:1989–1999. (PMID: 27230280488492010.1002/cam4.751)
      Qureshi R, Arora H, Rizvi MA (2015) EMT in cervical cancer: its role in tumour progression and response to therapy. Cancer Lett 356:321–331. (PMID: 2528147710.1016/j.canlet.2014.09.021)
      Glass CK, Natoli G (2016) Molecular control of activation and priming in macrophages. Nat Immunol 17:26–33. (PMID: 2668145910.1038/ni.3306)
      Gundra UM, Girgis NM, Ruckerl D, Jenkins S, Ward LN, Kurtz ZD et al (2014) Alternatively activated macrophages derived from monocytes and tissue macrophages are phenotypically and functionally distinct. Blood 123:e110-122. (PMID: 24695852402342710.1182/blood-2013-08-520619)
      Ivanova EA, Orekhov AN (2016) Monocyte activation in immunopathology: cellular test for development of diagnostics and therapy. J Immunol Res 2016:4789279. (PMID: 26885534473945910.1155/2016/4789279)
      Alvarado-Diaz CP, Nunez MT, Devoto L, Gonzalez-Ramos R (2015) Iron overload-modulated nuclear factor kappa-B activation in human endometrial stromal cells as a mechanism postulated in endometriosis pathogenesis. Fertil Steril 103:439–447. (PMID: 2550002210.1016/j.fertnstert.2014.10.046)
      Gupta S, Maitra A (2016) EMT: matter of life or death? Cell 164:840–842. (PMID: 2691942210.1016/j.cell.2016.02.024)
      Yu YQ, Liu LC, Wang FC, Liang Y, Cha DQ, Zhang JJ et al (2010) Induction profile of MANF/ARMET by cerebral ischemia and its implication for neuron protection. J Cereb Blood Flow Metab 30:79–91. (PMID: 1977380110.1038/jcbfm.2009.181)
      Chen YC, Sundvik M, Rozov S, Priyadarshini M, Panula P (2012) MANF regulates dopaminergic neuron development in larval zebrafish. Dev Biol 370:237–249. (PMID: 2289830610.1016/j.ydbio.2012.07.030)
      Yang W, Shen Y, Chen Y, Chen L, Wang L, Wang H et al (2014) Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis. J Neurol Sci 344:129–138. (PMID: 2500151410.1016/j.jns.2014.06.042)
      Lindholm P, Saarma M (2010) Novel CDNF/MANF family of neurotrophic factors. Dev Neurobiol 70:360–371. (PMID: 2018670410.1002/dneu.20760)
      Apostolou A, Shen Y, Liang Y, Luo J, Fang S (2008) Armet, a UPR-upregulated protein, inhibits cell proliferation and ER stress-induced cell death. Exp Cell Res 314:2454–2467. (PMID: 18561914671934010.1016/j.yexcr.2008.05.001)
      Wang C, Bao Q, Hou C, Sun M, Song X, Cao S et al (2021) Mono-macrophage-derived MANF alleviates bacterial myocarditis by Inhibiting NF-kappaB activation and myocardial inflammation. Inflammation 44:1916–1926. (PMID: 3393907010.1007/s10753-021-01469-0)
      Hou C, Mei Q, Song X, Bao Q, Li X, Wang D et al (2021) Mono-macrophage-derived MANF protects against lipopolysaccharide-induced acute kidney injury via inhibiting inflammation and renal M1 macrophages. Inflammation 44:693–703. (PMID: 3314562710.1007/s10753-020-01368-w)
      Sun T, Zhang X, Hou C, Yu S, Zhang Y, Yu Z et al (2022) Cold plasma irradiation attenuates atopic dermatitis via enhancing hif-1alpha-induced manf transcription expression. Front Immunol 13:941219. (PMID: 35911675932966610.3389/fimmu.2022.941219)
      Chen L, Feng L, Wang X, Du J, Chen Y, Yang W et al (2015) Mesencephalic astrocyte-derived neurotrophic factor is involved in inflammation by negatively regulating the NF-kappaB pathway. Sci Rep 5:8133. (PMID: 25640174431309810.1038/srep08133)
      Neves J, Zhu J, Sousa-Victor P, Konjikusic M, Riley R, Chew S et al (2016) Immune modulation by MANF promotes tissue repair and regenerative success in the retina. Science 353:aaf3646. (PMID: 27365452527051110.1126/science.aaf3646)
      Wang C, Yu S, Bao Q, Qiang W, Wu C, Zhang C et al (2020) Circulating mesencephalic astrocyte-derived neurotrophic factor negatively correlates with atrial apoptosis in human chronic atrial fibrillation. J Cardiovasc Pharmacol 75:141–147. (PMID: 3178988410.1097/FJC.0000000000000781)
      Shen SN, Wang LF, Jia YF, Hao YQ, Zhang L, Wang H (2013) Upregulation of microRNA-224 is associated with aggressive progression and poor prognosis in human cervical cancer. Diagn Pathol 8:69. (PMID: 23631806366137910.1186/1746-1596-8-69)
      Pecorelli S (2009) Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 105:103–104. (PMID: 1936768910.1016/j.ijgo.2009.02.012)
      Hou C, Wang D, Li X, He Y, Wei C, Jiang R et al (2019) MANF regulates splenic macrophage differentiation in mice. Immunol Lett 212:37–45. (PMID: 3122635910.1016/j.imlet.2019.06.007)
      Helm O, Held-Feindt J, Schafer H, Sebens S (2014) M1 and M2: there is no “good” and “bad”—how macrophages promote malignancy-associated features in tumorigenesis. Oncoimmunology 3:e946818. (PMID: 25610733429221510.4161/21624011.2014.946818)
      Visan I (2022) Inflammatory macrophages. Nat Immunol 23:988. (PMID: 35764718)
      Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867. (PMID: 12490959280303510.1038/nature01322)
      Pires BRB, Mencalha AL, Ferreira GM, de Souza WF, Morgado-Díaz JA, Maia AM et al (2017) NF-kappaB Is involved in the regulation of EMT genes in breast. Cancer Cells 12:e0169622.
      Kalluri R (2009) EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 119:1417–1419. (PMID: 19487817268912210.1172/JCI39675)
      Lopez-Novoa JM, Nieto MA (2009) Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med 1:303–314. (PMID: 20049734337814310.1002/emmm.200900043)
      Zhang T, Ma C, Zhang Z, Zhang H, Hu H (2020) NF-kappaB signaling in inflammation and cancer. MedComm 2021(2):618–653.
      Dong W, Sun S, Cao X, Cui Y, Chen A, Li X et al (2017) Exposure to TNF-alpha combined with TGF-beta induces carcinogenesis in vitro via NF-kappaB/Twist axis. Oncol Rep 37:1873–1882. (PMID: 2809887510.3892/or.2017.5369)
      Song R, Song H, Liang Y, Yin D, Zhang H, Zheng T et al (2014) Reciprocal activation between ATPase inhibitory factor 1 and NF-kappaB drives hepatocellular carcinoma angiogenesis and metastasis. Hepatology 60:1659–1673. (PMID: 2504286410.1002/hep.27312)
      Liu S, Shi L, Wang Y, Ye D, Ju H, Ma H et al (2018) Stabilization of slug by NF-kappab is essential for TNF-alpha -induced migration and epithelial-mesenchymal transition in head and neck squamous cell carcinoma cells. Cell Physiol Biochem 47:567–578. (PMID: 2979447410.1159/000489990)
      Nieto MA, Huang RY, Jackson RA, Thiery JP (2016) Emt: 2016. Cell 166:21–45. (PMID: 2736809910.1016/j.cell.2016.06.028)
      Casas E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ, Yang J (2011) Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res 71:245–254. (PMID: 21199805302580310.1158/0008-5472.CAN-10-2330)
      Sleeman JP, Thiery JP (2011) SnapShot: The epithelial-mesenchymal transition. Cell 145(162):e161.
      Farzanehpour M, Faghihloo E, Salimi V, Jalilvand S, Akhavan S, Muhammadnejad A et al (2020) Comparison of snail1, ZEB1, E-cadherin expression levels in HPV-induced cervical cancer. Iran J Public Health 49:2179–2188. (PMID: 337087397917501)
      Liu J, Wu Z, Han D, Wei C, Liang Y, Jiang T et al (2020) Mesencephalic astrocyte-derived neurotrophic factor inhibits liver cancer through small ubiquitin-related modifier (sumo)ylation-related suppression of nf-kappab/snail signaling pathway and epithelial-mesenchymal transition. Hepatology 71:1262–1278. (PMID: 3146942810.1002/hep.30917)
      Hou C, Wang D, Zhao M, Ballar P, Zhang X, Mei Q et al (2023) MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis. Acta Pharm Sin B 13:4234–4252. (PMID: 377993871054796410.1016/j.apsb.2023.07.027)
      Cho U, Kim B, Kim S, Han Y, Song YS (2018) Pro-inflammatory M1 macrophage enhances metastatic potential of ovarian cancer cells through NF-kappaB activation. Mol Carcinog 57:235–242. (PMID: 2902404210.1002/mc.22750)
      Luo Y, Mo D, Guo H, Ye C, Chen B, Zhu H et al (2022) NF-kappaB inactivation attenuates the M1 macrophage polarization in experimental necrotizing enterocolitis by glutaredoxin-1 deficiency. Cell Biol Int 46:1886–1899. (PMID: 3587017010.1002/cbin.11861)
    • Contributed Indexing:
      Keywords: Cervical cancer; Macrophage differentiation; Mesencephalic astrocyte-derived neurotrophic factor; Nuclear factor-kappa B
    • Accession Number:
      0 (MANF protein, human)
      0 (Nerve Growth Factors)
      0 (NF-kappa B)
    • Publication Date:
      Date Created: 20240512 Date Completed: 20240512 Latest Revision: 20240708
    • Publication Date:
      20240709
    • Accession Number:
      10.1007/s11033-024-09602-6
    • Accession Number:
      38735002