The melanoma brain metastatic microenvironment: aldolase C partakes in shaping the malignant phenotype of melanoma cells - a case of inter-tumor heterogeneity.
Animals
Biological Variation, Population
/ genetics
Brain Neoplasms
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Cell Survival
/ genetics
Fructose-Bisphosphate Aldolase
/ genetics
HEK293 Cells
Humans
Male
Melanoma
/ genetics
Mice
Mice, Inbred BALB C
Mice, Nude
Phenotype
Skin Neoplasms
/ genetics
Tumor Microenvironment
/ genetics
aldolase C
brain metastasis
melanoma
microglia
tumor microenvironment
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
22
10
2020
received:
30
09
2020
accepted:
01
12
2020
pubmed:
5
12
2020
medline:
1
4
2022
entrez:
4
12
2020
Statut:
ppublish
Résumé
Previous studies indicated that microglia cells upregulate the expression of aldolase C (ALDOC) in melanoma cells. The present study using brain-metastasizing variants from three human melanomas explores the functional role of ALDOC in the formation and maintenance of melanoma brain metastasis (MBM). ALDOC overexpression impacted differentially the malignant phenotype of these three variants. In the first variant, ALDOC overexpression promoted cell viability, adhesion to and transmigration through a layer of brain endothelial cells, and amplified brain micrometastasis formation. The cross-talk between this MBM variant and microglia cells promoted the proliferation and migration of the latter cells. In sharp contrast, ALDOC overexpression in the second brain-metastasizing melanoma variant reduced or did not affect the same malignancy features. In the third melanoma variant, ALDOC overexpression augmented certain characteristics of malignancy and reduced others. The analysis of biological functions and disease pathways in the ALDOC overexpressing variants clearly indicated that ALDOC induced the expression of tumor progression promoting genes in the first variant and antitumor progression properties in the second variant. Overall, these results accentuate the complex microenvironment interactions between microglia cells and MBM, and the functional impact of intertumor heterogeneity. Since intertumor heterogeneity imposes a challenge in the planning of cancer treatment, we propose to employ the functional response of tumors with an identical histology, to a particular drug or the molecular signature of this response, as a predictive indicator of response/nonresponse to this drug.
Identifiants
pubmed: 33274599
doi: 10.1002/1878-0261.12872
pmc: PMC8096793
doi:
Substances chimiques
Fructose-Bisphosphate Aldolase
EC 4.1.2.13
Banques de données
RefSeq
['NM_005165']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1376-1390Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Références
Nat Rev Cancer. 2020 Jan;20(1):4-11
pubmed: 31780784
Clin Exp Metastasis. 2018 Aug;35(5-6):369-378
pubmed: 29722001
J Intern Med. 2014 Jul;276(1):41-51
pubmed: 24661605
Cancer Chemother Pharmacol. 1989;24(3):148-54
pubmed: 2544306
Oncotarget. 2017 Jul 5;8(44):75778-75796
pubmed: 29100268
Neuro Oncol. 2004 Apr;6(2):154-65
pubmed: 15134630
PLoS One. 2014 Jan 27;9(1):e86679
pubmed: 24475166
Int J Mol Sci. 2018 Mar 24;19(4):
pubmed: 29587367
Cancer. 1991 Apr 15;67(8):2153-8
pubmed: 2004336
BMC Cancer. 2018 Feb 20;18(1):207
pubmed: 29463225
J Cell Physiol. 2019 Apr;234(4):3307-3320
pubmed: 30362507
Int J Cancer. 2019 Feb 15;144(4):802-817
pubmed: 29992556
Pharmacol Res. 2016 May;107:42-47
pubmed: 26924126
Trends Endocrinol Metab. 2018 Aug;29(8):549-559
pubmed: 29907340
Cell Physiol Biochem. 2017;42(1):397-406
pubmed: 28558381
Am J Pathol. 2010 Jun;176(6):2958-71
pubmed: 20382702
Trends Cancer. 2015 Sep;1(1):76-91
pubmed: 28741564
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Head Neck. 2016 Apr;38 Suppl 1:E1075-85
pubmed: 26565993
Int J Cancer. 2015 Mar 15;136(6):1296-307
pubmed: 25046141
J Biol Chem. 2012 Dec 14;287(51):42554-63
pubmed: 23093405
J Pathol. 2015 May;236(1):116-27
pubmed: 25639230
Cancer Treat Res. 2016;167:1-15
pubmed: 26601857
Nat Rev Cancer. 2018 Jun;18(6):359-376
pubmed: 29700396
J Biol Chem. 2006 Jan 20;281(3):1324-31
pubmed: 16278221
Cancers (Basel). 2019 Aug 23;11(9):
pubmed: 31450822
J Neuroinflammation. 2015 May 29;12:106
pubmed: 26022493
Front Immunol. 2017 Dec 08;8:1617
pubmed: 29276510
Exp Cell Res. 2020 Sep 1;394(1):112118
pubmed: 32502493
Mol Cancer. 2013 Dec 03;12:152
pubmed: 24298908
Curr Drug Metab. 2015;16(3):221-42
pubmed: 26504932
Clin Cancer Res. 2015 Mar 15;21(6):1258-66
pubmed: 25770293
Front Immunol. 2015 May 26;6:249
pubmed: 26074918
Cancer Med. 2013 Apr;2(2):155-63
pubmed: 23634283
Genomics. 2004 Dec;84(6):1014-20
pubmed: 15533718
Hum Vaccin Immunother. 2012 Aug;8(8):1143-5
pubmed: 22854659
Biochem Biophys Res Commun. 2018 Mar 4;497(2):639-645
pubmed: 29453983
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Curr Opin Cell Biol. 2005 Oct;17(5):559-64
pubmed: 16098726
Int J Cancer. 2012 Sep 1;131(5):1071-82
pubmed: 22025079
PLoS One. 2010 May 03;5(5):e10431
pubmed: 20454659
Proteomics. 2011 Jun;11(11):2275-82
pubmed: 21548097
Cancer Metastasis Rev. 2015 Dec;34(4):775-96
pubmed: 26573921
FASEB J. 2014 Nov;28(11):4591-609
pubmed: 25138157
J Oncol Pract. 2016 Jun;12(6):536-42
pubmed: 27288470
Mol Cancer. 2014 Jul 04;13:164
pubmed: 24993527
Nat Commun. 2016 May 03;7:11499
pubmed: 27139776
Drug Metab Pharmacokinet. 2016 Feb;31(1):35-45
pubmed: 26822993
Cells. 2020 Jul 13;9(7):
pubmed: 32668704