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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2020

01-12-2020 | Glioblastoma | Research

Crosstalk between microglia and patient-derived glioblastoma cells inhibit invasion in a three-dimensional gelatin hydrogel model

Authors: Jee-Wei Emily Chen, Jan Lumibao, Sarah Leary, Jann N. Sarkaria, Andrew J. Steelman, H. Rex Gaskins, Brendan A. C. Harley

Published in: Journal of Neuroinflammation | Issue 1/2020

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Abstract

Background

Glioblastoma is the most common and deadly form of primary brain cancer, accounting for more than 13,000 new diagnoses annually in the USA alone. Microglia are the innate immune cells within the central nervous system, acting as a front-line defense against injuries and inflammation via a process that involves transformation from a quiescent to an activated phenotype. Crosstalk between GBM cells and microglia represents an important axis to consider in the development of tissue engineering platforms to examine pathophysiological processes underlying GBM progression and therapy.

Methods

This work used a brain-mimetic hydrogel system to study patient-derived glioblastoma specimens and their interactions with microglia. Here, glioblastoma cells were either cultured alone in 3D hydrogels or in co-culture with microglia in a manner that allowed secretome-based signaling but prevented direct GBM-microglia contact. Patterns of GBM cell invasion were quantified using a three-dimensional spheroid assay. Secretome and transcriptome (via RNAseq) were used to profile the consequences of GBM-microglia interactions.

Results

Microglia displayed an activated phenotype as a result of GBM crosstalk. Three-dimensional migration patterns of patient-derived glioblastoma cells showed invasion was significantly decreased in response to microglia paracrine signaling. Potential molecular mechanisms underlying with this phenotype were identified from bioinformatic analysis of secretome and RNAseq data.

Conclusion

The data demonstrate a tissue engineered hydrogel platform can be used to investigate crosstalk between immune cells of the tumor microenvironment related to GBM progression. Such multi-dimensional models may provide valuable insight to inform therapeutic innovations to improve GBM treatment.
Appendix
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Literature
1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA. 2019;69:7–34.PubMed
2.
Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, Villano JL. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarker Prev. 2014;23:1985–96.CrossRef
3.
Zhang J, Stevens MF, Bradshaw TD. Temozolomide: mechanisms of action, repair and resistance. Curr Mol Pharmacol. 2012;5:102–14.PubMedCrossRef
4.
de Groot JF, Fuller G, Kumar AJ, Piao Y, Eterovic K, Ji Y, Conrad CA. Tumor invasion after treatment of glioblastoma with bevacizumab: radiographic and pathologic correlation in humans and mice. Neuro-Oncology. 2010;12:233–42.PubMedPubMedCentralCrossRef
5.
Anne C, Catherine G, Rogatien F, Clément T, Alice B, Laurent L, Audrey R, Tony A, Cécile H, Olivier C, Philippe M. Glioblastoma-associated stromal cells (GASCs) from histologically normal surgical margins have a myofibroblast phenotype and angiogenic properties. J Pathol. 2014;233:74–88.CrossRef
6.
Paolillo M, Boselli C, Schinelli S. Glioblastoma under siege: an overview of current therapeutic strategies. Brain Sci. 2018;8:15.PubMedCentralCrossRef
7.
Johnson DR, O’Neill BP. Glioblastoma survival in the United States before and during the temozolomide era. Journal of Neuro-Oncology. 2012;107:359–64.PubMedCrossRef
8.
Jackson C, Ruzevick J, Phallen J, Belcaid Z, Lim M. Challenges in immunotherapy presented by the glioblastoma multiforme microenvironment. Clin Dev Immunol. 2011;2011:732413.PubMedPubMedCentralCrossRef
9.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJB, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. New Eng J Med. 2005;352:987–96.PubMedCrossRef
10.
Mehta AI, Linninger A, Lesniak MS, Engelhard HH. Current status of intratumoral therapy for glioblastoma. J Neuro Oncol. 2015;125:1–7.CrossRef
11.
Cantrell JN, Waddle MR, Rotman M, Peterson JL, Ruiz-Garcia H, Heckman MG, Quinones-Hinojosa A, Rosenfeld SS, Brown PD, Trifiletti DM. Progress toward long-term survivors of glioblastoma. Mayo Clin Proceed. 2019;94:1278–86.CrossRef
12.
Cohen MH, Johnson JR, Pazdur R. Food and drug administration drug approval summary: temozolomide plus radiation therapy for the treatment of newly diagnosed glioblastoma multiforme. Clin Cancer Res. 2005;11:6767–71.PubMedCrossRef
13.
Liu Y, Hao S, Yu L, Gao Z. Long-term temozolomide might be an optimal choice for patient with multifocal glioblastoma, especially with deep-seated structure involvement: a case report and literature review. World J Surg Oncol. 2015;13:142.PubMedPubMedCentralCrossRef
14.
Wallner KE, Galicich JH, Krol G, Arbit E, Malkin MG. Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Rad Oncol Biol Phys. 1989;16:1405–9.CrossRef
15.
Delgado-López PD, Corrales-García EM. Survival in glioblastoma: a review on the impact of treatment modalities. Clin Transl Oncol. 2016;18:1062–71.PubMedCrossRef
16.
Choucair AK, Levin VA, Gutin PH, Davis RL, Silver P, Edwards MSB, Wilson CB. Development of multiple lesions during radiation therapy and chemotherapy in patients with gliomas. J Neurosurg. 1986;65:654–8.PubMedCrossRef
17.
Kirkpatrick JP, Sampson JH. Recurrent Malignant Gliomas. Seminars Rad Oncol. 2014;24:289–98.CrossRef
18.
Tait MJ, Petrik V, Loosemore A, Bell BA, Papadopoulos MC. Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases. Br J Neurosurg. 2007;21:496–500.PubMedCrossRef
19.
20.
Roesch S, Rapp C, Dettling S, Herold-Mende C. When immune cells turn bad-tumor-associated microglia/macrophages in glioma. Int J Mol Sci. 2018;19:436.PubMedCentralCrossRef
21.
22.
23.
Zhang M, Hutter G, Kahn SA, Azad TD, Gholamin S, Xu CY, Liu J, Achrol AS, Richard C, Sommerkamp P, et al. Anti-CD47 treatment stimulates phagocytosis of glioblastoma by M1 and M2 polarized macrophages and promotes M1 polarized macrophages in vivo. PLOS ONE. 2016;11:e0153550.PubMedPubMedCentralCrossRef
24.
Mignogna C, Signorelli F, Vismara MFM, Zeppa P, Camastra C, Barni T, Donato G, Di Vito A. A reappraisal of macrophage polarization in glioblastoma: Histopathological and immunohistochemical findings and review of the literature. Pathol Res Pract. 2016;212:491–9.PubMedCrossRef
25.
26.
Matias D, Balça-Silva J, da Graça GC, Wanjiru CM, Macharia LW, Nascimento CP, Roque NR, Coelho-Aguiar JM, Pereira CM, Dos Santos MF, et al. Microglia/astrocytes–glioblastoma crosstalk: crucial molecular mechanisms and microenvironmental factors. Front Cell Neurosci. 2018;12:235.PubMedPubMedCentralCrossRef
27.
28.
Lewis-Tuffin LJ, Rodriguez F, Giannini C, Scheithauer B, Necela BM, Sarkaria JN, Anastasiadis PZ. Misregulated E-cadherin expression associated with an aggressive brain tumor phenotype. PLOS ONE. 2010;5:e13665.PubMedPubMedCentralCrossRef
29.
Sivakumar H, Strowd R, Skardal A. Exploration of dynamic elastic modulus changes on glioblastoma cell populations with aberrant EGFR expression as a potential therapeutic intervention using a tunable hyaluronic acid hydrogel platform. Gels. 2017;3(3):28.PubMedCentralCrossRef
30.
Chen J-WE, Pedron S, Harley BAC. The combined influence of hydrogel stiffness and matrix-bound hyaluronic acid content on glioblastoma invasion. Macromolecular Bioscience. 2017;17:1700018.CrossRef
31.
Chen J-WE, Pedron S, Shyu P, Hu Y, Sarkaria JN, Harley BAC. Influence of hyaluronic acid transitions in tumor microenvironment on glioblastoma malignancy and invasive behavior. Front Mater. 2018;5:39.
32.
Chen J-WE, Lumibao J, Blazek A, Gaskins HR, Harley B. Hypoxia activates enhanced invasive potential and endogenous hyaluronic acid production by glioblastoma cells. Biomater Sci. 2018;6:854–62.PubMedPubMedCentralCrossRef
33.
Ngo MT, Karvelis E, Harley BAC. Multidimensional hydrogel models reveal endothelial network angiocrine signals increase glioblastoma cell number, invasion, and temozolomide resistance. Integr Biol. 2020;12:139–49.CrossRef
34.
Sarkaria JN, Carlson BL, Schroeder MA, Grogan P, Brown PD, Giannini C, Ballman KV, Kitange GJ, Guha A, Pandita A, James CD. Use of an orthotopic xenograft model for assessing the effect of epidermal growth factor receptor amplification on glioblastoma radiation response. Clin Cancer Res. 2006;12:2264–71.PubMedCrossRef
35.
Sarkaria JN, Yang L, Grogan PT, Kitange GJ, Carlson BL, Schroeder MA, Galanis E, Giannini C, Wu W, Dinca EB, James CD. Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Mol Cancer Therapeutics. 2007;6:1167–74.CrossRef
36.
Soto-Díaz K, Juda MB, Blackmore S, Walsh C, Steelman AJ. TAK1 inhibition in mouse astrocyte cultures ameliorates cytokine-induced chemokine production and neutrophil migration. J Neurochem. 2019;152:697–709.PubMedCrossRef
37.
Pedron S, Becka E, Harley BAC. Regulation of glioma cell phenotype in 3D matrices by hyaluronic acid. Biomaterials. 2013;34:7408–17.PubMedCrossRef
38.
Hopperton KE, Mohammad D, Trépanier MO, Giuliano V, Bazinet RP. Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review. Mol Psychiatry. 2018;23:177–98.PubMedCrossRef
39.
Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics (Oxford, England). 2010;26:139–40.CrossRef
40.
41.
Patro R, Duggal G, Love MI, Irizarry RA, Kingsford C. Salmon provides fast and bias-aware quantification of transcript expression. Nat Method. 2017;14:417–9.CrossRef
42.
Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995;57:289–300.
43.
44.
Chen Y, Lun A, Smyth G. From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline [version 2; peer review: 5 approved]. F1000Research. 2016;5:1438.
45.
Gentleman RC, Carey VJ, Bates DM, Bolstad B, Dettling M, Dudoit S, Ellis B, Gautier L, Ge Y, Gentry J, et al. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol. 2004;5:R80.PubMedPubMedCentralCrossRef
46.
Janky R, Verfaillie A, Imrichová H, Van de Sande B, Standaert L, Christiaens V, Hulselmans G, Herten K, Naval Sanchez M, Potier D, et al. iRegulon: from a gene list to a gene regulatory network using large motif and track collections. PLOS Comput Biol. 2014;10:e1003731.PubMedPubMedCentralCrossRef
47.
Maere S, Heymans K, Kuiper M. BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics. 2005;21:3448–9.PubMedCrossRef
48.
Chen J-W, Blazek A, Lumibao J, Gaskins HR, Harley BAC. Hypoxia activates enhanced invasive potential and endogenous hyaluronic acid production by glioblastoma cells. Biomater Sci. 2018;6:854–62.PubMedPubMedCentralCrossRef
49.
Chen J-WE, Pedron S, Shyu P, Hu Y, Sarkaria JN, Harley BAC. Influence of hyaluronic acid transitions in tumor microenvironment on glioblastoma malignancy and invasive behavior. Front Mater. 2018;5.
50.
Chen J-W, Pedron S, Harley BAC. The combined influence of hydrogel stiffness and matrix-bound hyaluronic acid content on glioblastoma invasion. Macromol Biosci. 2017;17:1700018.CrossRef
51.
Pedron S, Becka E, Harley BA. Spatially Gradated Hydrogel Platform as a 3D Engineered Tumor Microenvironment. Adv Mater. 2015;27:1567–72.PubMedCrossRef
52.
Pedron S, Wolter GL, Chen J-WE, Laken SE, Sarkaria JN, Harley BAC. Hyaluronic acid-functionalized gelatin hydrogels reveal extracellular matrix signals temper the efficacy of erlotinib against patient-derived glioblastoma specimens. Biomaterials. 2019;219:119371.PubMedPubMedCentralCrossRef
53.
Pedron S, Harley BAC. The impact of the biophysical features of a 3D gelatin microenvironment on glioblastoma malignancy. J Biomed Mater Res Pt A. 2013;101:3405–15.CrossRef
54.
Richbourg N, Wancura M, Gilchrist AE, Toubbeh S, Harley BAC, Cosgriff-Hernandez E, Peppas NA. Hydrogel synthesis conditions control swelling and predict stiffness and solute diffusivity. in revision; 2020.
55.
Gilchrist AE, Lee S, Hu Y, Harley BAC. Soluble signals and remodeling in a synthetic gelatin-based hematopoietic stem cell niche. Adv Healthc Mater. 2019;8:1900751.CrossRef
56.
Barnhouse V, Petrikas N, Crosby C, Zoldan J, BAC H. Perivascular secretome influences hematopoietic stem cell maintenance in a gelatin hydrogel. Ann Biomed Eng. 2020.
57.
Ngo MT, Karvelis E, Harley BAC. Multidimensional hydrogel models reveal endothelial network angiocrine signals increase glioblastoma cell number, invasion, and temozolomide resistance. Integr Biol (Camb). 2020;12:139–49.CrossRef
58.
Zambuto SG, Serrano JF, Vilbert AC, Lu Y, Harley BAC, Pedron S. Response of neuroglia to hypoxia-induced oxidative stress using enzymatically crosslinked hydrogels. MRS Communications. 2020;10:83–90.PubMedCrossRef
59.
Pogoda K, Chin L, Georges PC, Byfield FJ, Bucki R, Kim R, Weaver M, Wells RG, Marcinkiewicz C, Janmey PA. Compression stiffening of brain and its effect on mechanosensing by glioma cells. New J Phys. 2014;16:075002.PubMedPubMedCentralCrossRef
60.
Budday S, Nay R, de Rooij R, Steinmann P, Wyrobek T, Ovaert TC, Kuhl E. Mechanical properties of gray and white matter brain tissue by indentation. J Mechanic Behavior of Biomedical Materials. 2015;46:318–30.CrossRef
61.
Giese A, Loo MA, Tran N, Haskett D, Coons SW, Berens ME. Dichotomy of astrocytoma migration and proliferation. Int J Cancer. 1996;67:275–82.PubMedCrossRef
62.
Lemstra AW, JCM G i’t W, JJM H, van Haastert ES, AJM R, Eikelenboom P, van Gool WA. Microglia activation in sepsis: a case-control study. J Neuroinflamm. 2007;4:4.CrossRef
63.
Wang Z, Gerstein M, Snyder M. RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Gene. 2009;10:57–63.CrossRef
64.
Oliveira AI, Anjo SI, Vieira de Castro J, Serra SC, Salgado AJ, Manadas B, Costa BM. Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells. Cell Commun Signal. 2017;15:37.PubMedPubMedCentralCrossRef
65.
Hatzikirou H, Basanta D, Simon M, Schaller K, Deutsch A. 'Go or grow': the key to the emergence of invasion in tumour progression? Math Med Biol. 2012;29:49–65.PubMedCrossRef
66.
Fukata M, Vamadevan AS, Abreu MT. Toll-like receptors (TLRs) and Nod-like receptors (NLRs) in inflammatory disorders. Seminar Immunol. 2009;21:242–53.CrossRef
67.
Kim YK, Shin JS, Nahm MH. NOD-like receptors in infection, immunity, and diseases. Yonsei Med J. 2016;57:5–14.PubMedCrossRef
68.
Tarassishin L, Casper D, Lee SC. Aberrant expression of interleukin-1β and inflammasome activation in human malignant gliomas. PLOS ONE. 2014;9:e103432.PubMedPubMedCentralCrossRef
69.
Ryuto M, Ono M, Izumi H, Yoshida S, Weich HA, Kohno K, Kuwano M. Induction of vascular endothelial growth factor by tumor necrosis factor α in human glioma cells: possible roles of SP-1. J Biol Chem. 1996;271:28220–8.PubMedCrossRef
70.
Hayden MS, Ghosh S. Regulation of NF-κB by TNF family cytokines. Seminar Immunol. 2014;26:253–66.CrossRef
71.
Chandrika G, Natesh K, Ranade D, Chugh A, Shastry P. Suppression of the invasive potential of Glioblastoma cells by mTOR inhibitors involves modulation of NFκB and PKC-α signaling. Sci Rep. 2016;6:22455.PubMedPubMedCentralCrossRef
72.
Town T, Nikolic V, Tan J. The microglial "activation" continuum: from innate to adaptive responses. J Neuroinflam. 2005;2:24.CrossRef
73.
74.
Wang F, Zhang P, Yang L, Yu X, Ye X, Yang J, Qian C, Zhang X, Cui YH, Bian XW. Activation of toll-like receptor 2 promotes invasion by upregulating MMPs in glioma stem cells. Am J Transl Res. 2015;7:607–15.PubMedPubMedCentral
75.
Flamant F, Cheng S-Y, Hollenberg AN, Moeller LC, Samarut J, Wondisford FE, Yen PM, Refetoff S. Thyroid hormone signaling pathways: time for a more precise nomenclature. Endocrinology. 2017;158:2052–7.PubMedPubMedCentralCrossRef
76.
Davis FB, Tang HY, Shih A, Keating T, Lansing L, Hercbergs A, Fenstermaker RA, Mousa A, Mousa SA, Davis PJ, Lin HY. Acting via a cell surface receptor, thyroid hormone is a growth factor for glioma cells. Cancer Res. 2006;66:7270–5.PubMedCrossRef
77.
78.
Page BDG, Fletcher S, Yue P, Li Z, Zhang X, Sharmeen S, Datti A, Wrana JL, Trudel S, Schimmer AD, et al. Identification of a non-phosphorylated, cell permeable, small molecule ligand for the Stat3 SH2 domain. Bioorganic Med Chem Letters. 2011;21:5605–9.CrossRef
79.
Zhang J, Xu S, Xu J, Li Y, Zhang J, Zhang J, Lu X. miR-767-5p inhibits glioma proliferation and metastasis by targeting SUZ12. Oncol Rep. 2019;42:55–66.PubMedPubMedCentral
80.
Martín-Pérez D, Sánchez E, Maestre L, Suela J, Vargiu P, Di Lisio L, Martínez N, Alves J, Piris MA, Sánchez-Beato M. Deregulated expression of the polycomb-group protein SUZ12 target genes characterizes mantle cell lymphoma. Am J Pathol. 2010;177:930–42.PubMedPubMedCentralCrossRef
81.
Kamal MM, Sathyan P, Singh SK, Zinn PO, Marisetty AL, Liang S, Gumin J, El-Mesallamy HO, Suki D, Colman H, et al. REST regulates oncogenic properties of glioblastoma stem cells. Stem Cells. 2012;30:405–14.PubMedPubMedCentralCrossRef
82.
Filatova A, Acker T, Garvalov BK. The cancer stem cell niche(s): The crosstalk between glioma stem cells and their microenvironment. Biochimica et Biophysica Acta (BBA) - General Subjects. 2013;1830:2496–508.CrossRef
83.
Sakariassen PØ, Immervoll H, Chekenya M. Cancer stem cells as mediators of treatment resistance in brain tumors: status and controversies. Neoplasia (New York, NY). 2007;9:882–92.CrossRef
84.
Mori T, Anazawa Y, Iiizumi M, Fukuda S, Nakamura Y, Arakawa H. Identification of the interferon regulatory factor 5 gene (IRF-5) as a direct target for p53. Oncogene. 2002;21:2914–8.PubMedCrossRef
85.
Bi X, Hameed M, Mirani N, Pimenta EM, Anari J, Barnes BJ. Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis. Breast Cancer Res. 2011;13:R111.PubMedPubMedCentralCrossRef
86.
Ni D, Ma X, Li HZ, Gao Y, Li XT, Zhang Y, Ai Q, Zhang P, Song EL, Huang QB, et al. Downregulation of FOXO3a promotes tumor metastasis and is associated with metastasis-free survival of patients with clear cell renal cell carcinoma. Clin Cancer Res. 2014;20:1779–90.PubMedCrossRef
87.
88.
Qian Z, Ren L, Wu D, Yang X, Zhou Z, Nie Q, Jiang G, Xue S, Weng W, Qiu Y, Lin Y. Overexpression of FoxO3a is associated with glioblastoma progression and predicts poor patient prognosis. Int J Cancer. 2017;140:2792–804.PubMedCrossRef
89.
Chang AL, Miska J, Wainwright DA, Dey M, Rivetta CV, Yu D, Kanojia D, Pituch KC, Qiao J, Pytel P, et al. CCL2 produced by the glioma microenvironment is essential for the recruitment of regulatory T cells and myeloid-derived suppressor cells. Cancer Res. 2016;76:5671–82.PubMedPubMedCentralCrossRef
90.
Vakilian A, Khorramdelazad H, Heidari P, Sheikh Rezaei Z, Hassanshahi G. CCL2/CCR2 signaling pathway in glioblastoma multiforme. Neurochem Int. 2017;103:1–7.PubMedCrossRef
91.
Guan E, Wang J, Norcross MA. Identification of human macrophage inflammatory proteins 1α and 1β as a native secreted heterodimer. J Biol Chem. 2001;276:12404–9.PubMedCrossRef
92.
Gill ZP, Perks CM, Newcomb PV, Holly JM. Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem. 1997;272:25602–7.PubMedCrossRef
93.
Watanabe K, Uemura K, Asada M, Maesako M, Akiyama H, Shimohama S, Takahashi R, Kinoshita A. The participation of insulin-like growth factor-binding protein 3 released by astrocytes in the pathology of Alzheimer's disease. Mol Brain. 2015;8:82.PubMedPubMedCentralCrossRef
94.
Kielczewski JL, Hu P, Shaw LC, Li Calzi S, Mames RN, Gardiner TA, McFarland E, Chan-Ling T, Grant MB. Novel protective properties of IGFBP-3 result in enhanced pericyte ensheathment, reduced microglial activation, increased microglial apoptosis, and neuronal protection after ischemic retinal injury. Am J Pathol. 2011;178:1517–28.PubMedPubMedCentralCrossRef
95.
Matteucci E, Giampietro O. Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme. Curr Med Chem. 2009;16:2943–51.PubMedCrossRef
96.
Stremenova J, Krepela E, Mares V, Trim J, Dbaly V, Marek J, Vanickova Z, Lisa V, Yea C, Sedo A. Expression and enzymatic activity of dipeptidyl peptidase-IV in human astrocytic tumours are associated with tumour grade. Int J Oncol. 2007;31:785–92.PubMed
97.
Pethiyagoda CL, Welch DR, Fleming TP. Dipeptidyl peptidase IV (DPPIV) inhibits cellular invasion of melanoma cells. Clin Exp Metastasis. 2000;18:391–400.PubMedCrossRef
98.
F. Riordan J. [16] - Angiogenin. In: Methods in Enzymology. Volume 341. Edited by Nicholson AW: Academic Press; 2001. p. 263–73.
99.
100.
DeCoster MA, Schabelman E, Tombran-Tink J, Bazan NG. Neuroprotection by pigment epithelial-derived factor against glutamate toxicity in developing primary hippocampal neurons. J Neurosci Res. 1999;56:604–10.PubMedCrossRef
101.
Doll JA, Stellmach VM, Bouck NP, Bergh AR, Lee C, Abramson LP, Cornwell ML, Pins MR, Borensztajn J, Crawford SE. Pigment epithelium-derived factor regulates the vasculature and mass of the prostate and pancreas. Nat Med. 2003;9:774–80.PubMedCrossRef
102.
Filleur S, Nelius T, de Riese W, Kennedy RC. Characterization of PEDF: a multi-functional serpin family protein. J Cell Biochem. 2009;106:769–75.PubMedCrossRef
103.
Guan M, Pang C-P, Yam H-F, Cheung K-F, Liu W-W, Lu Y. Inhibition of glioma invasion by overexpression of pigment epithelium-derived factor. Cancer Gene Ther. 2004;11:325–32.PubMedCrossRef
104.
Shinozaki Y, Shibata K, Yoshida K, Shigetomi E, Gachet C, Ikenaka K, Tanaka KF, Koizumi S. Transformation of astrocytes to a neuroprotective phenotype by microglia via P2Y1 receptor downregulation. Cell Rep. 2017;19:1151–64.PubMedCrossRef
105.
Gilchrist AE, Harley BAC. Connecting secretome to hematopoietic stem cell phenotype shifts in an engineered bone marrow niche. Integr Biol (Camb). 2020;12(7):175–87.PubMedCrossRefPubMedCentral
106.
Abels ER, Maas SLN, Nieland L, Wei Z, Cheah PS, Tai E, Kolsteeg CJ, Dusoswa SA, Ting DT, Hickman S, et al. Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21. Cell Rep. 2019;28:3105–19 e3107.PubMedPubMedCentralCrossRef
107.
Wei J, Gabrusiewicz K, Heimberger A. The controversial role of microglia in malignant gliomas. Clin Dev Immunol. 2013;2013:12.CrossRef
108.
Charles NA, Holland EC, Gilbertson R, Glass R, Kettenmann H. The brain tumor microenvironment. Glia. 2011;59:1169–80.PubMedCrossRef
109.
Binda E, Visioli A, Reynolds B, Vescovi AL. Heterogeneity of cancer-initiating cells within glioblastoma. Front Biosci (Schol Ed). 2012;4:1235–48.
110.
Reynolds BA, Vescovi AL. Brain cancer stem cells: think twice before going flat. Cell Stem Cell. 2009;5:466–7.PubMedCrossRef
111.
112.
Uemae Y, Ishikawa E, Osuka S, Matsuda M, Sakamoto N, Takano S, Nakai K, Yamamoto T, Matsumura A. CXCL12 secreted from glioma stem cells regulates their proliferation. J Neurooncol. 2014;117:43–51.PubMedCrossRef
113.
Sun L, Hui AM, Su Q, Vortmeyer A, Kotliarov Y, Pastorino S, Passaniti A, Menon J, Walling J, Bailey R, et al. Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 2006;9:287–300.PubMedCrossRef
114.
Baysan M, Woolard K, Bozdag S, Riddick G, Kotliarova S, Cam MC, Belova GI, Ahn S, Zhang W, Song H, et al. Micro-environment causes reversible changes in DNA methylation and mRNA expression profiles in patient-derived glioma stem cells. PLoS One. 2014;9:e94045.PubMedPubMedCentralCrossRef
115.
Binda E, Reynolds BA, Vescovi AL. Glioma stem cells: turpis omen in nomen? (The evil in the name?). J Intern Med. 2014;276:25–40.PubMedCrossRef
116.
Lemke D, Weiler M, Blaes J, Wiestler B, Jestaedt L, Klein AC, Low S, Eisele G, Radlwimmer B, Capper D, et al. Primary glioblastoma cultures: can profiling of stem cell markers predict radiotherapy sensitivity? J Neurochem. 2014;131:251–64.PubMedCrossRef
117.
118.
Wiranowska MR, M. V.: Extracellular matrix microenvironment in glioma progression. In Glioma - Exploring Its Biology and Practical Relevance. Edited by Ghosh A: InTech; 2011: 257-284.
Metadata
Title
Crosstalk between microglia and patient-derived glioblastoma cells inhibit invasion in a three-dimensional gelatin hydrogel model
Authors
Jee-Wei Emily Chen
Jan Lumibao
Sarah Leary
Jann N. Sarkaria
Andrew J. Steelman
H. Rex Gaskins
Brendan A. C. Harley
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2020
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-020-02026-6

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