The impact of initial tumor microenvironment on imaging phenotype.
Animals
Brain
/ diagnostic imaging
Brain Neoplasms
/ diagnosis
Collagen
/ administration & dosage
Drug Combinations
Female
Glioblastoma
/ diagnosis
Humans
Laminin
/ administration & dosage
Magnetic Resonance Imaging
Neoplastic Stem Cells
/ pathology
Proteoglycans
/ administration & dosage
Rats
Spheroids, Cellular
Tumor Cells, Cultured
Tumor Microenvironment
Xenograft Model Antitumor Assays
/ methods
Contrast enhancement
Glioblastoma
MRI
Matrigel
Neurospheres
PDOX models
Rat
Journal
Cancer treatment and research communications
ISSN: 2468-2942
Titre abrégé: Cancer Treat Res Commun
Pays: England
ID NLM: 101694651
Informations de publication
Date de publication:
2021
2021
Historique:
received:
20
10
2020
revised:
13
01
2021
accepted:
14
01
2021
pubmed:
12
2
2021
medline:
1
1
2022
entrez:
11
2
2021
Statut:
ppublish
Résumé
Models of human cancer, to be useful, must replicate human disease with high fidelity. Our focus in this study is rat xenograft brain tumors as a model of human embedded cerebral tumors. A distinguishing signature of such tumors in humans, that of contrast-enhancement on imaging, is often not present when the human cells grow in rodents, despite the xenografts having nearly identical DNA signatures to the original tumor specimen. Although contrast enhancement was uniformly evident in all the human tumors from which the xenografts' cells were derived, we show that long-term contrast enhancement in the model tumors may be determined conditionally by the tumor microenvironment at the time of cell implantation. We demonstrate this phenomenon in one of two patient-derived orthotopic xenograft (PDOX) models using cancer stem-like cell (CSC)-enriched neurospheres from human tumor resection specimens, transplanted to groups of immune-compromised rats in the presence or absence of a collagen/fibrin scaffolding matrix, Matrigel. The rats were imaged by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and their brains were examined by histopathology. Targeted proteomics of the PDOX tumor specimens grown from CSC implanted with and without Matrigel showed that while the levels of the majority of proteins and post-translational modifications were comparable between contrast-enhancing and non-enhancing tumors, phosphorylation of Fox038 showed a differential expression. The results suggest key proteins determine contrast enhancement and suggest a path toward the development of better animal models of human glioma. Future work is needed to elucidate fully the molecular determinants of contrast-enhancement.
Identifiants
pubmed: 33571801
pii: S2468-2942(21)00014-9
doi: 10.1016/j.ctarc.2021.100315
pmc: PMC8127413
mid: NIHMS1683858
pii:
doi:
Substances chimiques
Drug Combinations
0
Laminin
0
Proteoglycans
0
matrigel
119978-18-6
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100315Subventions
Organisme : NCI NIH HHS
ID : R01 CA218596
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Ltd.
Références
Magn Reson Med. 2018 Nov;80(5):2040-2052
pubmed: 29524243
Ann Oncol. 2017 Oct 1;28(10):2595-2605
pubmed: 28945830
Cell Stem Cell. 2009 Nov 6;5(5):527-39
pubmed: 19896443
Nat Rev Clin Oncol. 2019 Aug;16(8):509-520
pubmed: 30733593
Cancer Cell. 2007 Jan;11(1):69-82
pubmed: 17222791
J Neurooncol. 2012 Apr;107(2):359-64
pubmed: 22045118
Clin Adv Hematol Oncol. 2017 Nov;15(11):844-846
pubmed: 29200416
Nat Rev Cancer. 2015 May;15(5):311-6
pubmed: 25907221
Stem Cells. 2010 Feb;28(2):181-90
pubmed: 19937755
Br J Haematol. 2005 Feb;128(3):303-9
pubmed: 15667531
Gerontology. 2015;61(6):515-25
pubmed: 25832544
Cells. 2019 Sep 30;8(10):
pubmed: 31574953
N Engl J Med. 2005 Mar 10;352(10):987-96
pubmed: 15758009
Oncotarget. 2020 Jan 28;11(4):443-451
pubmed: 32064048
Clin Cancer Res. 2017 Mar 1;23(5):1177-1185
pubmed: 27733479
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16466-71
pubmed: 17056721
Cell. 2007 Jan 26;128(2):309-23
pubmed: 17254969
Oncol Rep. 2020 May;43(5):1619-1629
pubmed: 32323818
Front Oncol. 2015 Nov 16;5:251
pubmed: 26636033
Radiat Res. 2017 Jan;187(1):79-88
pubmed: 28001908
Cell Rep. 2013 Jan 31;3(1):260-73
pubmed: 23333277
Comp Med. 2017 Aug 1;67(4):300-314
pubmed: 28830577
Radiat Res. 2015 Jun;183(6):713-21
pubmed: 26010711
Nat Protoc. 2012 May 17;7(6):1138-44
pubmed: 22596226
Cancer Discov. 2014 Sep;4(9):998-1013
pubmed: 25185190
NMR Biomed. 2015 Nov;28(11):1557-69
pubmed: 26423316
Neuro Oncol. 2016 Apr;18(4):549-56
pubmed: 26823503
NMR Biomed. 2008 Oct;21(8):830-8
pubmed: 18613001
Semin Cancer Biol. 1993 Aug;4(4):259-65
pubmed: 8400148
Neuro Oncol. 2015 Nov;17 Suppl 6:vi1-26
pubmed: 26403167
Lancet Oncol. 2009 May;10(5):459-66
pubmed: 19269895
Biochem Pharmacol. 2013 Mar 1;85(5):612-622
pubmed: 23063412
Semin Oncol Nurs. 2018 Dec;34(5):443-453
pubmed: 30409553
J Natl Cancer Inst. 1991 Jun 5;83(11):769-74
pubmed: 1789823
Semin Cancer Biol. 2005 Oct;15(5):378-86
pubmed: 15975825
Nat Rev Cancer. 2006 Jun;6(6):425-36
pubmed: 16723989
Curr Protoc Pharmacol. 2011 Mar;Chapter 14:Unit 14.16
pubmed: 21743824
J Neurooncol. 2019 Jan;141(2):253-263
pubmed: 30446898
Cancer Chemother Pharmacol. 2018 Dec;82(6):945-952
pubmed: 30209569
J Neurosci Res. 2010 Feb 15;88(3):542-51
pubmed: 19774667
Cancer Cell Int. 2017 Dec 20;17:122
pubmed: 29296105
CNS Oncol. 2017 Jul;6(3):167-177
pubmed: 28718326
Sci Rep. 2020 Feb 13;10(1):2576
pubmed: 32054865
Neuro Oncol. 2012 Aug;14(8):979-93
pubmed: 22679124
Magn Reson Med. 2014 Jun;71(6):2206-14
pubmed: 23878070
Arch Immunol Ther Exp (Warsz). 2013 Feb;61(1):25-41
pubmed: 23224339
Adv Drug Deliv Rev. 2014 Dec 15;79-80:3-18
pubmed: 24997339
Nat Genet. 2018 May;50(5):708-717
pubmed: 29686388
Cancers (Basel). 2018 Dec 20;11(1):
pubmed: 30577488
J Clin Oncol. 2003 Apr 15;21(8):1624-36
pubmed: 12697889
Mol Imaging. 2016 May 05;15:
pubmed: 27151136
Neoplasia. 2014 Mar;16(3):193-206, 206.e19-25
pubmed: 24726753
Cell Mol Life Sci. 2018 Feb;75(3):385-402
pubmed: 28821904
Mol Cell Proteomics. 2009 Nov;8(11):2595-612
pubmed: 19674965
Cancer Discov. 2017 May;7(5):462-477
pubmed: 28331002
Nat Rev Mater. 2019 Oct;4(10):651-668
pubmed: 32647587
Neuro Oncol. 2015 Oct;17 Suppl 4:iv1-iv62
pubmed: 26511214
NMR Biomed. 2013 Aug;26(8):1028-41
pubmed: 23881857
J Vis Exp. 2014 Jan 07;(83):e51088
pubmed: 24429465