Suppression of CCL2 angiocrine function by adrenomedullin promotes tumor growth.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
02 01 2023
02 01 2023
Historique:
received:
30
07
2021
revised:
19
08
2022
accepted:
13
10
2022
entrez:
14
11
2022
pubmed:
15
11
2022
medline:
18
11
2022
Statut:
ppublish
Résumé
Within the tumor microenvironment, tumor cells and endothelial cells regulate each other. While tumor cells induce angiogenic responses in endothelial cells, endothelial cells release angiocrine factors, which act on tumor cells and other stromal cells. We report that tumor cell-derived adrenomedullin has a pro-angiogenic as well as a direct tumor-promoting effect, and that endothelium-derived CC chemokine ligand 2 (CCL2) suppresses adrenomedullin-induced tumor cell proliferation. Loss of the endothelial adrenomedullin receptor CALCRL or of the G-protein Gs reduced endothelial proliferation. Surprisingly, tumor cell proliferation was also reduced after endothelial deletion of CALCRL or Gs. We identified CCL2 as a critical angiocrine factor whose formation is inhibited by adrenomedullin. Furthermore, CCL2 inhibited adrenomedullin formation in tumor cells through its receptor CCR2. Consistently, loss of endothelial CCL2 or tumor cell CCR2 normalized the reduced tumor growth seen in mice lacking endothelial CALCRL or Gs. Our findings show tumor-promoting roles of adrenomedullin and identify CCL2 as an angiocrine factor controlling adrenomedullin formation by tumor cells.
Identifiants
pubmed: 36374225
pii: 213682
doi: 10.1084/jem.20211628
pmc: PMC9665902
pii:
doi:
Substances chimiques
Adrenomedullin
148498-78-6
Chemokine CCL2
0
Chemokines
0
Ligands
0
Receptors, CCR2
0
Ccl2 protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022 Nakayama et al.
Références
J Pept Sci. 2017 Jul;23(7-8):472-485
pubmed: 28150464
Am J Physiol. 1998 Jun;274(6):L1024-9
pubmed: 9609742
Cancer Cell. 2012 Jul 10;22(1):91-105
pubmed: 22789541
Front Cell Dev Biol. 2020 Aug 19;8:766
pubmed: 32974337
Cancers (Basel). 2012 Apr 11;4(2):400-19
pubmed: 24213317
Gut. 2017 Jan;66(1):157-167
pubmed: 26452628
Front Immunol. 2019 Dec 13;10:2759
pubmed: 31921102
J Clin Endocrinol Metab. 2012 May;97(5):1763-70
pubmed: 22419707
Sci Rep. 2017 Jan 16;7:40524
pubmed: 28091613
FASEB J. 2013 Feb;27(2):590-600
pubmed: 23099649
Cancer Res. 2016 Sep 15;76(18):5302-12
pubmed: 27488527
BMC Cancer. 2017 Jan 31;17(1):88
pubmed: 28143493
J Transl Med. 2014 Dec 05;12:339
pubmed: 25475159
Biochem Biophys Res Commun. 1993 Apr 30;192(2):553-60
pubmed: 8387282
Elife. 2019 Oct 03;8:
pubmed: 31580256
Angiogenesis. 2011 Dec;14(4):533-44
pubmed: 22045552
Nat Rev Cancer. 2017 Aug;17(8):457-474
pubmed: 28706266
Curr Opin Hematol. 2017 May;24(3):248-255
pubmed: 28178039
Oncoimmunology. 2017 Jun 19;6(8):e1334744
pubmed: 28919995
Oncotarget. 2017 Jul 4;8(27):44732-44748
pubmed: 28512254
J Immunol. 1993 Sep 1;151(5):2786-93
pubmed: 8360492
J Natl Cancer Inst. 2002 Aug 21;94(16):1226-37
pubmed: 12189226
Circ Res. 2004 Aug 20;95(4):415-23
pubmed: 15242974
Peptides. 2013 Apr;42:105-11
pubmed: 23340020
PLoS One. 2016 Apr 14;11(4):e0152789
pubmed: 27078157
Cardiovasc Res. 2012 Jul 1;95(1):7-18
pubmed: 22492672
Annu Rev Cell Dev Biol. 2011;27:563-84
pubmed: 21756109
FASEB J. 2003 Oct;17(13):1937-9
pubmed: 12897063
J Leukoc Biol. 1996 Jun;59(6):916-24
pubmed: 8691078
Mol Cell Biol. 1991 Jun;11(6):3125-31
pubmed: 2038321
Cell Mol Life Sci. 2015 Aug;72(16):3115-26
pubmed: 25953627
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):
pubmed: 33875597
Nat Rev Cancer. 2018 Jun;18(6):359-376
pubmed: 29700396
Clin Exp Metastasis. 2009;26(7):817-28
pubmed: 19629725
Development. 2016 Oct 1;143(19):3582-3590
pubmed: 27702786
Am J Pathol. 2012 Oct;181(4):1464-72
pubmed: 22841816
Oncogene. 2014 Jun 19;33(25):3217-24
pubmed: 23851506
Pharmacol Rev. 2002 Jun;54(2):233-46
pubmed: 12037140
Am J Pathol. 2013 Jun;182(6):2380-90
pubmed: 23562442
Trends Pharmacol Sci. 2020 Apr;41(4):249-265
pubmed: 32115276
J Biol Chem. 1996 Aug 23;271(34):20828-35
pubmed: 8702838
J Exp Med. 2009 Feb 16;206(2):411-20
pubmed: 19171764
J Clin Invest. 2019 Jun 17;129(7):2775-2791
pubmed: 31205027
Br J Cancer. 2006 Jan 16;94(1):1-7
pubmed: 16251875
Front Oncol. 2019 Apr 09;9:231
pubmed: 31024838
J Clin Invest. 2017 Feb 1;127(2):593-607
pubmed: 28094771
Stem Cells Dev. 2018 Apr 1;27(7):456-465
pubmed: 29415626
Cancer Res. 2004 Nov 1;64(21):7857-66
pubmed: 15520192
Cell. 2020 Jun 11;181(6):1346-1363.e21
pubmed: 32473126
Nat Rev Cancer. 2010 Feb;10(2):138-46
pubmed: 20094048
Science. 2017 Oct 20;358(6361):321-326
pubmed: 29051371
Front Oncol. 2021 Jan 06;10:589218
pubmed: 33489885
Cytokine Growth Factor Rev. 2010 Feb;21(1):41-8
pubmed: 20005149
Pharm Res. 1998 May;15(5):685-9
pubmed: 9619775
Cancers (Basel). 2019 Oct 09;11(10):
pubmed: 31600937
Endocr Rev. 2000 Apr;21(2):138-67
pubmed: 10782362
Oncogene. 2002 Apr 25;21(18):2815-21
pubmed: 11973640
Regul Pept. 2003 Apr 15;112(1-3):175-83
pubmed: 12667640
J Nephrol. 2003 Sep-Oct;16(5):673-81
pubmed: 14733413
Cancer Cell. 2011 Sep 13;20(3):300-14
pubmed: 21907922
J Interferon Cytokine Res. 1995 Jul;15(7):655-65
pubmed: 7553238
Cardiovasc Res. 2016 Sep;111(4):398-409
pubmed: 27307317
Am J Physiol Cell Physiol. 2002 May;282(5):C947-70
pubmed: 11940508
Clin Cancer Res. 2000 Jul;6(7):2808-14
pubmed: 10914728
Am J Respir Cell Mol Biol. 2011 Feb;44(2):230-7
pubmed: 20395632
Brain Behav Immun. 2011 May;25(4):787-99
pubmed: 21334428
JCI Insight. 2020 Dec 3;5(23):
pubmed: 33268595
Sci Adv. 2019 Sep 18;5(9):eaaw2778
pubmed: 31555726
Eur J Immunol. 1997 May;27(5):1091-7
pubmed: 9174597