An engineered glioblastoma model yields novel macrophage-secreted drivers of invasion.
Journal
bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187
Informations de publication
Date de publication:
19 Nov 2023
19 Nov 2023
Historique:
pubmed:
28
11
2023
medline:
28
11
2023
entrez:
28
11
2023
Statut:
epublish
Résumé
Glioblastomas (GBMs) are highly invasive brain tumors replete with brain- and blood-derived macrophages, collectively known as tumor-associated macrophages (TAMs). Targeting TAMs has been proposed as a therapeutic strategy but has thus far yielded limited clinical success in slowing GBM progression, due in part to an incomplete understanding of TAM function in GBM. Here, by using an engineered hyaluronic acid-based 3D invasion platform, patient-derived GBM cells, and multi-omics analysis of GBM tumor microenvironments, we show that M2-polarized macrophages stimulate GBM stem cell (GSC) mesenchymal transition and invasion. We identify TAM-derived transforming growth factor beta induced (TGFβI/BIGH3) as a pro-tumorigenic factor in the GBM microenvironment. In GBM patients, BIGH3 mRNA expression correlates with poor patient prognosis and is highest in the most aggressive GBM molecular subtype. Inhibiting TAM-derived BIGH3 signaling with a blocking antibody or small molecule inhibitor suppresses GSC invasion. Our work highlights the utility of 3D
Identifiants
pubmed: 38014161
doi: 10.1101/2023.11.18.567683
pmc: PMC10680873
pii:
doi:
Types de publication
Preprint
Langues
eng
Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA247970
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR025622
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214749
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA260443
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA227136
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA127001
Pays : United States
Déclaration de conflit d'intérêts
Competing Interests The authors declare no competing interests.
Références
Nat Cell Biol. 2015 May;17(5):678-88
pubmed: 25893917
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
ACS Biomater Sci Eng. 2019 Aug 12;5(8):3753-3765
pubmed: 31598545
Cell. 2019 Aug 8;178(4):835-849.e21
pubmed: 31327527
J Proteome Res. 2002 Jan-Feb;1(1):21-6
pubmed: 12643522
Front Immunol. 2022 Jun 30;13:888713
pubmed: 35844605
Nat Commun. 2015 Jul 22;6:7866
pubmed: 26198319
Nat Rev Immunol. 2023 Jul 4;:
pubmed: 37402992
Adv Healthc Mater. 2023 Jun;12(14):e2203143
pubmed: 36694362
J Neurooncol. 2018 Apr;137(2):395-407
pubmed: 29294230
Cancers (Basel). 2022 May 14;14(10):
pubmed: 35626034
Biomaterials. 2011 Nov;32(31):7913-23
pubmed: 21820737
J Exp Clin Cancer Res. 2019 Mar 22;38(1):117
pubmed: 30898166
Nat Commun. 2021 Feb 19;12(1):1151
pubmed: 33608526
Clin Cancer Res. 2020 Mar 1;26(5):1094-1104
pubmed: 31852831
Sci Adv. 2022 Jul 8;8(27):eabl5165
pubmed: 35857445
PLoS One. 2013 Aug 05;8(8):e69182
pubmed: 23940516
Glia. 2011 Aug;59(8):1169-80
pubmed: 21446047
J Clin Invest. 2023 Nov 16;:
pubmed: 37971886
Nature. 2012 Feb 22;485(7396):55-61
pubmed: 22367541
J Invest Dermatol. 1995 May;104(5):844-9
pubmed: 7738366
Neuron. 2019 Nov 6;104(3):442-449
pubmed: 31697921
Cancer Cell. 2017 Jul 10;32(1):42-56.e6
pubmed: 28697342
Nat Rev Immunol. 2011 Oct 25;11(11):750-61
pubmed: 22025054
Sci Rep. 2017 Feb 10;7:42088
pubmed: 28186196
Sci Signal. 2019 Nov 26;12(609):
pubmed: 31772123
Cell Physiol Biochem. 2018;49(3):1097-1109
pubmed: 30196284
Front Oncol. 2021 Aug 09;11:710695
pubmed: 34434898
Neuroimage. 2014 Apr 15;90:308-14
pubmed: 24368262
Neuro Oncol. 2013 Aug;15(8):1079-87
pubmed: 23828240
J Mech Behav Biomed Mater. 2015 Jun;46:318-30
pubmed: 25819199
Nat Neurosci. 2019 Dec;22(12):2098-2110
pubmed: 31740814
Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):E2595-604
pubmed: 22923691
Cell Rep. 2017 Oct 31;21(5):1399-1410
pubmed: 29091775
Annu Rev Physiol. 2017 Feb 10;79:541-566
pubmed: 27813830
Int Immunopharmacol. 2014 Nov;23(1):37-45
pubmed: 25130606
J Biol Chem. 2000 Oct 6;275(40):30907-15
pubmed: 10906123
Int J Biochem Cell Biol. 2007;39(12):2183-94
pubmed: 17659994
J Clin Invest. 2023 Jan 3;133(1):
pubmed: 36594466
Neuroimage. 2013 Oct 1;79:145-52
pubmed: 23644001
Adv Mater. 2021 Feb;33(5):e2004776
pubmed: 33326131
Nucleic Acids Res. 2012 Jan;40(Database issue):D1144-9
pubmed: 22086960
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Curr Protoc. 2021 Mar;1(3):e90
pubmed: 33780170
Brief Bioinform. 2021 Jul 20;22(4):
pubmed: 33147626
Cell Rep. 2019 Oct 15;29(3):589-602.e6
pubmed: 31618629
Trends Immunol. 2021 Apr;42(4):280-292
pubmed: 33663953
Neuro Oncol. 2017 Jan;19(1):139-141
pubmed: 28031383
Cancer Cell. 2013 Sep 9;24(3):331-46
pubmed: 23993863
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
BMC Bioinformatics. 2012 Jun 18;13:134
pubmed: 22708584
Curr Protoc Bioinformatics. 2007 Jan;Chapter 13:Unit 13.4
pubmed: 18428785
Nat Methods. 2008 Apr;5(4):319-22
pubmed: 18345006
Matrix Biol. 2020 Jan;85-86:128-146
pubmed: 31028838
Biomaterials. 2019 Feb;194:171-182
pubmed: 30605825
Neuropathol Appl Neurobiol. 2018 Feb;44(2):185-206
pubmed: 28767130
Cells. 2019 Sep 20;8(10):
pubmed: 31547193
APL Bioeng. 2018 Sep;2(3):
pubmed: 29855630
Cancer Cell. 2021 Jun 14;39(6):779-792.e11
pubmed: 34087162
Cancer Gene Ther. 2023 May;30(5):716-726
pubmed: 36599974
Biochem Pharmacol. 2006 Nov 30;72(11):1622-31
pubmed: 16846592
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Front Mater. 2018 Jun;5:
pubmed: 30581816
Nat Med. 2022 Apr;28(4):752-765
pubmed: 35411077
Nat Neurosci. 2021 Apr;24(4):595-610
pubmed: 33782623
Nat Neurosci. 2016 Jan;19(1):20-7
pubmed: 26713745
J Cell Biochem. 2013 Dec;114(12):2795-808
pubmed: 23836528
Nat Cancer. 2023 Sep;4(9):1273-1291
pubmed: 37460871
J Neuroinflammation. 2020 Nov 18;17(1):346
pubmed: 33208156
Nat Rev Mater. 2019 Oct;4(10):651-668
pubmed: 32647587
Cell Signal. 2021 Aug;84:110028
pubmed: 33940163
Nat Commun. 2022 Mar 18;13(1):1481
pubmed: 35304461
Genome Biol. 2017 Dec 20;18(1):234
pubmed: 29262845
Cancer Res. 2017 May 1;77(9):2266-2278
pubmed: 28235764
Brain Pathol. 2019 Jul;29(4):513-529
pubmed: 30506802
Front Immunol. 2022 Sep 08;13:970702
pubmed: 36159811
Nat Rev Immunol. 2019 Jun;19(6):369-382
pubmed: 30718830
Neuro Oncol. 2021 Oct 5;23(12 Suppl 2):iii1-iii105
pubmed: 34608945