Pivotal Role for Cxcr2 in Regulating Tumor-Associated Neutrophil in Breast Cancer.
Cxcr2
breast cancer
chemokine receptors
neutrophils
tumor microenvironment
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
25 May 2021
25 May 2021
Historique:
received:
16
04
2021
revised:
18
05
2021
accepted:
20
05
2021
entrez:
2
6
2021
pubmed:
3
6
2021
medline:
3
6
2021
Statut:
epublish
Résumé
Chemokines present in the tumor microenvironment are essential for the control of tumor progression. We show here that several ligands of the chemokine receptor Cxcr2 were up-regulated in the PyMT (polyoma middle T oncogene) model of breast cancer. Interestingly, the knock-down of Cxcr2 in PyMT animals led to an increased growth of the primary tumor and lung metastasis. The analysis of tumor content of PyMT-Cxcr2-/- animals highlighted an increased infiltration of tumor associated neutrophils (TANs), mirrored by a decreased recruitment of tumor associated macrophages (TAMs) compared to PyMT animals. Analysis of PyMT-Cxcr2-/- TANs revealed that they lost their killing ability compared to PyMT-Cxcr2+/+ TANs. The transcriptomic analysis of PyMT-Cxcr2-/- TANs showed that they had a more pronounced pro-tumor TAN2 profile compared to PyMT TANs. In particular, PyMT-Cxcr2-/- TANs displayed an up-regulation of the pathways involved in reactive oxygen species (ROS) production and angiogenesis and factors favoring metastasis, but reduced apoptosis. In summary, our data reveal that a lack of Cxcr2 provides TANs with pro-tumor effects.
Identifiants
pubmed: 34070438
pii: cancers13112584
doi: 10.3390/cancers13112584
pmc: PMC8197482
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES023513
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES030419
Pays : United States
Organisme : Ligue Contre le Cancer
ID : X
Références
Nat Neurosci. 2010 Mar;13(3):319-26
pubmed: 20154684
Blood. 2003 Nov 15;102(10):3562-8
pubmed: 12893769
Ther Adv Hematol. 2020 Sep 14;11:2040620720958586
pubmed: 32973988
Oncoimmunology. 2015 Jul 28;5(1):e1061175
pubmed: 26942073
J Clin Invest. 2014 Dec;124(12):5466-80
pubmed: 25384214
Int J Cancer. 2015 Feb 1;136(3):572-83
pubmed: 24806531
Cancer Cell. 2016 Jun 13;29(6):832-845
pubmed: 27265504
Blood. 1994 Sep 15;84(6):1737-46
pubmed: 7521686
Clin Cancer Res. 2009 Nov 15;15(22):6820-9
pubmed: 19887480
Cold Spring Harb Perspect Biol. 2020 Jul 1;12(7):
pubmed: 31767647
Sci Immunol. 2020 Feb 21;5(44):
pubmed: 32086381
Signal Transduct Target Ther. 2020 Aug 25;5(1):166
pubmed: 32843638
Biochim Biophys Acta. 2016 Dec;1866(2):290-299
pubmed: 27750042
Trends Mol Med. 2010 Mar;16(3):133-44
pubmed: 20163989
Cancer Res. 2009 Aug 15;69(16):6747-55
pubmed: 19679556
J Exp Med. 2001 Mar 19;193(6):727-40
pubmed: 11257139
Cancers (Basel). 2021 May 12;13(10):
pubmed: 34066060
PLoS One. 2013 Aug 28;8(8):e72249
pubmed: 24015224
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Nat Med. 2008 Dec;14(12):1384-9
pubmed: 19029987
Mediators Inflamm. 2015;2015:701067
pubmed: 26648665
Int J Oncol. 2003 Apr;22(4):765-71
pubmed: 12632066
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
J Immunol. 2008 Oct 1;181(7):4666-75
pubmed: 18802069
Histol Histopathol. 2000 Apr;15(2):523-37
pubmed: 10809374
Clin Cancer Res. 2005 Jun 1;11(11):4117-27
pubmed: 15930347
Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10578-82
pubmed: 1359541
Front Immunol. 2016 Jan 11;6:652
pubmed: 26793192
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21248-55
pubmed: 21081700
Biochim Biophys Acta Rev Cancer. 2019 Apr;1871(2):289-312
pubmed: 30703432
J Exp Med. 2008 Sep 29;205(10):2235-49
pubmed: 18809714
Int J Cancer. 2016 Apr 15;138(8):1982-93
pubmed: 26619320
Oncotarget. 2015 Oct 6;6(30):29034-47
pubmed: 26362269
J Immunol. 1999 Feb 15;162(4):2341-6
pubmed: 9973513
Neoplasia. 2014 Oct 23;16(10):771-88
pubmed: 25379015
Cold Spring Harb Perspect Biol. 2018 Aug 1;10(8):
pubmed: 28778871
Nat Rev Cancer. 2020 Sep;20(9):485-503
pubmed: 32694624
Cancer Immunol Res. 2016 Nov;4(11):968-982
pubmed: 27737879
Cell. 2009 Dec 24;139(7):1315-26
pubmed: 20064377
Cell Metab. 2009 Apr;9(4):339-49
pubmed: 19356715
J Leukoc Biol. 2018 Mar;103(3):457-464
pubmed: 29345348
Endocr Relat Cancer. 2007 Dec;14(4):1039-52
pubmed: 18045955
Proc Natl Acad Sci U S A. 2015 Feb 10;112(6):E566-75
pubmed: 25624500
Nat Rev Cancer. 2009 Apr;9(4):239-52
pubmed: 19279573
Immunity. 2000 Feb;12(2):121-7
pubmed: 10714678
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Prostate. 2006 Dec 1;66(16):1721-8
pubmed: 16941672
J Clin Invest. 2012 Sep;122(9):3127-44
pubmed: 22922255
Bioinformatics. 2002 Jan;18(1):207-8
pubmed: 11836235
J Immunol. 2009 May 1;182(9):5693-701
pubmed: 19380816
Nature. 2015 Jun 18;522(7556):345-348
pubmed: 25822788
Breast Cancer Res. 2007;9(1):R15
pubmed: 17261184
Carcinogenesis. 2012 May;33(5):949-55
pubmed: 22425643
Nature. 2007 Dec 6;450(7171):825-31
pubmed: 18064003
Cancer Cell. 2009 Sep 8;16(3):183-94
pubmed: 19732719
Nature. 2002 Dec 19-26;420(6917):860-7
pubmed: 12490959
Oncogene. 2003 Jan 16;22(2):256-65
pubmed: 12527894
J Invest Dermatol. 2000 Aug;115(2):234-44
pubmed: 10951241
Int J Mol Sci. 2019 Jun 06;20(11):
pubmed: 31174392
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12493-8
pubmed: 16891410
J Clin Invest. 2009 Jun;119(6):1571-82
pubmed: 19451693
J Clin Invest. 2010 Apr;120(4):1151-64
pubmed: 20237412
J Immunol. 2000 Nov 1;165(9):5269-77
pubmed: 11046061
Science. 1994 Jul 29;265(5172):682-4
pubmed: 8036519
Cancer Res. 2006 Jan 1;66(1):259-66
pubmed: 16397239
Cancer Res. 2012 Aug 15;72(16):3919-27
pubmed: 22751466
Life Sci Alliance. 2020 Feb 10;3(3):
pubmed: 32041848
Int J Cancer. 2014 Mar 15;134(6):1346-58
pubmed: 24154944
J Clin Invest. 2013 Jul 1;:
pubmed: 23863628
J Immunol. 2004 Mar 1;172(5):2853-60
pubmed: 14978086
Mol Cell Biol. 1992 Mar;12(3):954-61
pubmed: 1312220
Cell. 2012 Jul 6;150(1):165-78
pubmed: 22770218
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2640-5
pubmed: 18268320
Oncoimmunology. 2014 Jun 25;3:e29256
pubmed: 25101223
Nat Immunol. 2010 Oct;11(10):889-96
pubmed: 20856220
Cancers (Basel). 2020 Jul 27;12(8):
pubmed: 32727083
J Biol Chem. 1992 Aug 15;267(23):16283-7
pubmed: 1379593
J Immunol. 2005 Oct 15;175(8):5351-7
pubmed: 16210641
J Cell Physiol. 2013 Jul;228(7):1404-12
pubmed: 23065796
Immunity. 2019 May 21;50(5):1317-1334.e10
pubmed: 30979687
Annu Rev Pathol. 2014;9:181-218
pubmed: 24050624
Cancer Immunol Res. 2021 Feb;9(2):200-213
pubmed: 33177110
Oncoimmunology. 2016 Sep 13;5(11):e1232221
pubmed: 27999744
Cancer Cell. 2013 Nov 11;24(5):631-44
pubmed: 24229710
Mol Cancer Ther. 2013 May;12(5):799-808
pubmed: 23468530
Nat Rev Immunol. 2012 Mar 22;12(4):253-68
pubmed: 22437938