AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.3146
Submit to GPD
Cite this article
62
Download
1055
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Perineural invasion in prostate cancer is associated with Schwann cells and disruption of circadian rhythm-related gene expression: A bioinformatics approach

Sérgio Lopes Silva1 ,  Genilda Castro de Omena Neta1 ,  Rodger Marcel Lima Rocha1 ,  Ana Kelly da Silva Fernandes Duarte1 ,  Carlos Alberto de Carvalho Fraga1*
Show Less
1 Complex of Medical and Nursing Sciences, Federal University of Alagoas, Campus Arapiraca, Arapiraca, Alagoas, Brazil
GPD 2024, 3(3), 3146 https://doi.org/10.36922/gpd.3146
Submitted: 12 March 2024 | Accepted: 22 April 2024 | Published: 9 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

Schwann cells in the tumor microenvironment are reportedly involved in the production of several factors that benefit cancer cell growth. During this process, Schwann cells are dedifferentiated and facilitate cancer cellular proliferation. The cells then migrate to the region close to the tumor tissue and assist the development of the neoplastic cells. Accordingly, the present study was designed to evaluate the perineural invasion in prostate cancer, in association with disrupted circadian rhythm-related gene expression in Schwann cells. Initially, we identified a database reporting gene expression in Schwann cells in a neoplastic context from the GEO Datasets platform in the GEO repository. The database contains the expression results from experiments in which two factors produced by tumor cells were added to cell cultures. Comparisons were made between samples from the first and third passages. Then, these data were used in differential gene expression analysis and combined with differential expression data of genes upregulated in perineural invasion-negative and -positive prostate cancers. We observed that the “axon guidance” pathway was upregulated in perineural invasion-negative prostate cancers. Meanwhile, upregulated mRNAs activated the “axon guidance” pathway and, together with ROBO1 and MPZ upregulation, inhibited perineural invasion pathways. Both genes are also associated with inhibition of Schwann cell migration. PER3, NR3C1, PPARGC1A, TIMP3, ID2, PDE6B, and CAVIN1 were upregulated in perineural invasion-negative tumors, while SLC25A10 was upregulated. We also observed upregulated expression in perineural invasion-positive tumors for genes such as PPARGC1A, TIMP3, S100A8, ID2, DEFB1, AQP3, ASS1, PDE6B, NEFH, and CAVIN1. AQP3 and NEFH were upregulated only in perineural invasion-positive tumors and PER3 and NR3C1 were upregulated only in perineural invasion-negative samples. The findings revealed that circadian rhythm and/or melatonin disruption are associated with dedifferentiation of Schwann cells, which consequently produce a set of factors that drive tumor progression. These processes may also be involved in tumor invasion into the perineural tissue in prostate cancer.

Keywords
Bioinformatics
Prostate adenocarcinoma
Clock-related genes
Schwann cell dedifferentiation
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
References
  1. Gatenby RA, Gillies RJ. A microenvironmental model of carcinogenesis. Nat Rev Cancer. 2008;8:56-61. doi: 10.1038/nrc2255

 

  1. Lo HC, Zhang XHF. EMT in metastasis: Finding the right balance. Dev Cell. 2018;45:663-665. doi: 10.1016/j.devcel.2018.05.033

 

  1. Binmadi NO, Basile JR. Perineural Invasion in Oral Squamous Cell Carcinoma: A Discussion of Significance and Review of the Literature. Vol. 47. Netherlands: Elsevier Ltd.; 2011. doi: 10.1016/j.oraloncology.2011.08.002

 

  1. Aguilar-Cazares D, Chavez-Dominguez R, Carlos- Reyes A, Lopez-Camarillo C, Hernadez de la Cruz ON, Lopez-Gonzalez JS. Contribution of angiogenesis to inflammation and cancer. Front Oncol. 2019;9:1399. doi: 10.3389/FONC.2019.01399

 

  1. De Paula AMB, Souza LR, Farias LC, et al. Analysis of 724 cases of primary head and neck squamous cell carcinoma (HNSCC) with a focus on young patients and p53 immunolocalization. Oral Oncol. 2009;45:777-782. doi: 10.1016/j.oraloncology.2008.11.015

 

  1. de Carvalho Fraga CA, Farias LC, de Oliveira MVM, et al. Increased VEGFR2 and MMP9 protein levels are associated with epithelial dysplasia grading. Pathol Res Pract. 2014;210:959-964. doi: 10.1016/J.PRP.2014.06.020

 

  1. Poswar FDO, Fraga CADC, Gomes ESB, et al. Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma. Int J Surg Pathol. 2015;23:20-25. doi: 10.1177/1066896914540998

 

  1. Hingorani DV, Lippert CN, Crisp JL, et al. Impact of MMP-2 and MMP-9 enzyme activity on wound healing, tumor growth and RACPP cleavage. PLoS One. 2018;13:e0198464. doi: 10.1371/journal.pone.0198464

 

  1. Huang CY, Chang YM, Shih YT, et al. Schwann cell migration induced by earthworm extract via activation of PAs and MMP2/9 mediated through ERK1/2 and p38. Evid Based Complement Alternat Med. 2011;2011:395458. doi: 10.1093/ecam/nep131

 

  1. Deborde S, Omelchenko T, Lyubchik A, et al. Schwann cells induce cancer cell dispersion and invasion. J Clin Invest. 2016;126:1538-1554. doi: 10.1172/JCI82658

 

  1. Fraga CADC, De Oliveira MVM, De Oliveira ES, et al. A high HIF-1α expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients. Oral Oncol. 2012;48:130-135. doi: 10.1016/j.oraloncology.2011.08.023

 

  1. Yao Q, Kou L, Tu Y, Zhu L. MMP-responsive “smart” drug delivery and tumor targeting. Trends Pharmacol Sci. 2018;39:766-781. doi: 10.1016/j.tips.2018.06.003

 

  1. Braakhuis BJM, Brakenhoff RH, Leemans CR. Head and neck cancer: Molecular carcinogenesis. Ann Oncol. 2005;16 Suppl 2:ii249-ii250. doi: 10.1093/ANNONC/MDI713

 

  1. Zee PC, Attarian H, Videnovic A. Circadian rhythm abnormalities. Continuum (Minneap Minn). 2013;19: 132-147. doi: 10.1212/01.CON.0000427209.21177.aa

 

  1. Barbosa Vieira TK, Jurema da Rocha Leão M, Pereira LX, et al. Correlation between circadian rhythm related genes, type 2 diabetes, and cancer: Insights from metanalysis of transcriptomics data. Mol Cell Endocrinol. 2021;526:111214. doi: 10.1016/J.MCE.2021.111214

 

  1. Rana S, Mahmood S. Circadian rhythm and its role in malignancy. J Circadian Rhythms. 2010;8:3. doi: 10.1186/1740-3391-8-3

 

  1. Zhou Y, Shurin GV, Zhong H, Bunimovich YL, Han B, Shurin MR. Schwann cells augment cell spreading and metastasis of lung cancer. Cancer Res. 2018;78:5927-5939. doi: 10.1158/0008-5472.CAN-18-1702

 

  1. Deborde S, Wong RJ. How Schwann cells facilitate cancer progression in nerves. Cell Mol Life Sci. 2017;74:4405-4420. doi: 10.1007/s00018-017-2578-x

 

  1. Azam SH, Pecot CV. Cancer’s got nerve: Schwann cells drive perineural invasion. J Clin Invest. 2016;126:1242-4. doi: 10.1172/JCI86801

 

  1. Poswar FDO, Farias LC, Fraga CADC, et al. Bioinformatics, interaction network analysis, and neural networks to characterize gene expression of radicular cyst and periapical granuloma. J Endod. 2015;41:877-883. doi: 10.1016/j.joen.2015.02.004

 

  1. Colaprico A, Silva TC, Olsen C, et al. TCGAbiolinks: An R/Bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 2016;44:e71. doi: 10.1093/nar/gkv1507

 

  1. Silva TC, Colaprico A, Olsen C, et al. TCGAbiolinksGUI: A graphical user interface to analyze cancer molecular and clinical data. F1000Research. 2018;7:439. doi: 10.12688/f1000research.14197.1

 

  1. Edgar R, Lash A. The gene expression omnibus (GEO): A gene expression and hybridization repository. Nucleic Acids Res. 2002;30:207-210. doi: 10.1093/nar/30.1.207

 

  1. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44-57. doi: 10.1038/nprot.2008.211

 

  1. Li T, Fan J, Wang B, et al. TIMER: A web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017;77:e108-e110. doi: 10.1158/0008-5472.CAN-17-0307

 

  1. Bunimovich YL, Keskinov AA, Shurin GV, Shurin MR. Schwann cells: A new player in the tumor microenvironment. Cancer Immunol Immunother. 2017;66:959. doi: 10.1007/S00262-016-1929-Z

 

  1. Webber CA, Christie KJ, Cheng C, et al. Schwann cells direct peripheral nerve regeneration through the Netrin-1 receptors, DCC and Unc5H2. Glia. 2011;59:1503-1517. doi: 10.1002/glia.21194

 

  1. Li Z, Zhou J, Zhang J, Li S, Wang H, Du J. Cancer-associated fibroblasts promote PD-L1 expression in mice cancer cells via secreting CXCL5. Int J Cancer. 2019;145:1946-1957. doi: 10.1002/ijc.32278

 

  1. Nagarajan D, McArdle SEB. Immune landscape of breast cancers. Biomedicines. 2018;11:20. doi: 10.3390/biomedicines6010020

 

  1. Movahedi K, Laoui D, Gysemans C, et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res. 2010;70:5728-5739. doi: 10.1158/0008-5472.CAN-09-4672

 

  1. Clements MP, Byrne E, Camarillo Guerrero LF, et al. The wound microenvironment reprograms Schwann cells to invasive mesenchymal-like cells to drive peripheral nerve regeneration. Neuron. 2017;96:98-114.e7. doi: 10.1016/j.neuron.2017.09.008

 

  1. Wang JJ, Lei KF, Han F. Tumor microenvironment: Recent advances in various cancer treatments. Eur Rev Med Pharmacol Sci. 2018;22:3855-3864. doi: 10.26355/eurrev-201806-15270

 

  1. Zhang X, Patterson TA, Paule MG, Wang C, Slikker W. Schwann cells. In: Neural Cell Biology. Boca Raton: CRC Press; 2017. doi: 10.1201/9781315370491

 

  1. Kim HS, Lee J, Lee DY, et al. Schwann cell precursors from human pluripotent stem cells as a potential therapeutic target for myelin repair. Stem Cell Reports. 2017;8: 1714-1726. doi: 10.1016/j.stemcr.2017.04.011

 

  1. Santos EMS, Guimarães TA, Santos HO, et al. Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma. Tumor Biol. 2017;39:1010428317699130. doi: 10.1177/1010428317699130

 

  1. Guimaraes TA, Farias LC, Fraga CA, et al. Evaluation of the antineoplastic activity of gallic acid in oral squamous cell carcinoma under hypoxic conditions. Anticancer Drugs. 2016;27:407-416. doi: 10.1097/CAD.0000000000000342

 

  1. Noguti J, Moura CFG, Jesus GPP, et al. Metastasis from oral cancer: An overview. Cancer Genomics Proteomics. 2012;9:329-35.

 

  1. Islam F, Gopalan V, Lam AKY, Kabir SR. Pea lectin inhibits cell growth by inducing apoptosis in SW480 and SW48 cell lines. Int J Biol Macromol. 2018;117:1050-1057. doi: 10.1016/j.ijbiomac.2018.06.021

 

  1. Rashmi R, DeSelm C, Helms C, et al. AKT inhibitors promote cell death in cervical cancer through disruption of mTOR signaling and glucose uptake. PLoS One. 2014;9:e92948. doi: 10.1371/journal.pone.0092948

 

  1. Ren C, Chen X, Du N, et al. Low-intensity pulsed ultrasound promotes Schwann cell viability and proliferation via the GSK-3β/β-catenin signaling pathway. Int J Biol Sci. 2018;14:497-507. doi: 10.7150/ijbs.22409

 

  1. Domenech-Estevez E, Baloui H, Meng X, et al. Akt regulates axon wrapping and myelin sheath thickness in the PNS. J Neurosci. 2016;36:4506-1521. doi: 10.1523/JNEUROSCI.3521-15.2016

 

  1. Carr L, Parkinson DB, Dun XP. Expression patterns of Slit and Robo family members in adult mouse spinal cord and peripheral nervous system. PLoS One. 2017;12:e0172736. doi: 10.1371/journal.pone.0172736

 

  1. Gohrig A, Detjen KM, Hilfenhaus G, et al. Axon guidance factor SLIT2 inhibits neural invasion and metastasis in pancreatic cancer. Cancer Res. 2014;74:1529-1540. doi: 10.1158/0008-5472.CAN-13-1012

 

  1. Wang LJ, Zhao Y, Han B, et al. Targeting Slit-Roundabout signaling inhibits tumor angiogenesis in chemical-induced squamous cell carcinogenesis. Cancer Sci. 2008;29:510-517. doi: 10.1111/j.1349-7006.2007.00721.x

 

  1. Qin F, Zhang H, Ma L, et al. Low expression of Slit2 and robo1 is associated with poor prognosis and brain-specific metastasis of breast cancer patients. Sci Rep. 2015;5:14430. doi: 10.1038/srep14430

 

  1. Gara RK, Kumari S, Ganju A, Yallapu MM, Jaggi M, Chauhan SC. Slit/Robo pathway: A promising therapeutic target for cancer. Drug Discov Today. 2015;20:156-164. doi: 10.1016/j.drudis.2014.09.008

 

  1. Zhu S, Ge J, Liu Z, et al. Circadian rhythm influences the promoting role of pulsed electromagnetic fields on sciatic nerve regeneration in rats. Front Neurol. 2017;8:101. doi: 10.3389/FNEUR.2017.00101

 

  1. Tiong YL, Ng KY, Koh RY, Ponnudurai G, Chye SM. Melatonin promotes Schwann cell dedifferentiation and proliferation through the Ras/Raf/ERK and MAPK pathways, and glial cell-derived neurotrophic factor expression. Exp Ther Med. 2020;20:16. doi: 10.3892/ETM.2020.9143
Share
Back to top
Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept