Targeting claudin-4 enhances chemosensitivity in breast cancer.
Animals
Antibodies
/ pharmacology
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Breast Neoplasms
/ drug therapy
Carcinoma, Ductal, Breast
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Claudin-1
Claudin-4
/ chemistry
Drug Synergism
Female
Humans
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Paclitaxel
/ pharmacology
Tamoxifen
/ pharmacology
Triple Negative Breast Neoplasms
/ drug therapy
Tumor Microenvironment
/ drug effects
Xenograft Model Antitumor Assays
breast cancer
chemotherapy
claudin
microenvironment
tight junction
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
May 2020
May 2020
Historique:
received:
31
10
2019
revised:
05
02
2020
accepted:
16
02
2020
pubmed:
23
2
2020
medline:
2
6
2020
entrez:
23
2
2020
Statut:
ppublish
Résumé
Triple negative breast cancer (TNBC) is characterized by highly aggressive phenotype, limited treatment options and a poor prognosis. In the present study, we examined the therapeutic effect of anti-claudin (CLDN)-4 extracellular domain antibody, 4D3, on TNBC. When the expression of CLDN4 and CLDN1 in invasive ductal carcinoma (IDC) was examined in 114 IDC (78 cases from 2004 to 2009 in a single center and 36 cases of tissues array), CLDN1 had lower expression than CLDN4 and was correlated with histological grade. In contrast, expression of CLDN4 was correlated with histological grade, receptor subtype, and stage. CLDN4 expression in human IDC cell lines MCF-7 (luminal subtype) and MDA-468 (TNBC) was at the same level. In both cells, paclitaxel (PTX)-induced growth suppression was enhanced by 4D3. Furthermore, 4D3 increased both intracellular PTX concentration (in both cells) and apoptosis. In the mouse model, 4D3 promoted the antitumor effect of PTX on subcutaneous tumors and reduced lung metastasis. The combination of PTX and 4D3 reduced M2 macrophages and mesenchymal stem cells in the tumor. 4D3 also reduced stemness of the tumors and increased the intratumoral pH. Moreover, concurrent treatment with 4D3, PTX and tamoxifen, or with PTX and tamoxifen in MDA-468 also showed the same level of antitumor activity and survival as MCF-7. Furthermore, in a bone metastasis model, combination of PTX and bisphosphonate with 4D3 promoted tumor growth in both cells. Thus, CLDN4 targeting of the antibody facilitated existing therapeutic effects.
Identifiants
pubmed: 32086991
doi: 10.1111/cas.14361
pmc: PMC7226188
doi:
Substances chimiques
Antibodies
0
CLDN1 protein, human
0
CLDN4 protein, human
0
Claudin-1
0
Claudin-4
0
Tamoxifen
094ZI81Y45
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1840-1850Subventions
Organisme : Natural Science Foundation of Jiangsu Education Department Project
ID : 17KJB320010
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 16H05164
Organisme : Ministry of Education, Culture, Sports, Science and Technology
ID : 17K19923
Organisme : National Natural Science Foundation of China
ID : 81702723
Informations de copyright
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Oncol Rep. 2019 Jun;41(6):3155-3166
pubmed: 31002367
Breast. 2010 Oct;19(5):312-21
pubmed: 20382530
Cancer Lett. 2015 Dec 1;369(1):212-21
pubmed: 26342407
Breast Cancer. 2011 Jul;18(3):165-73
pubmed: 21290263
Cancer Res. 2000 Nov 15;60(22):6281-7
pubmed: 11103784
Ann N Y Acad Sci. 2017 Jun;1397(1):80-99
pubmed: 28636799
PLoS One. 2017 Sep 25;12(9):e0185566
pubmed: 28945801
J Pathol. 2002 Feb;196(2):163-70
pubmed: 11793367
Science. 1956 Aug 10;124(3215):269-70
pubmed: 13351639
Cell Commun Signal. 2018 Jan 5;16(1):2
pubmed: 29329589
Br J Cancer. 1993 Dec;68(6):1104-9
pubmed: 7903152
Clin Cancer Res. 2003 Jul;9(7):2567-75
pubmed: 12855632
Ther Adv Med Oncol. 2019 Sep 27;11:1758835919875324
pubmed: 31632466
Gastroenterology. 2001 Sep;121(3):678-84
pubmed: 11522752
Oncotarget. 2018 Dec 21;9(100):37367-37378
pubmed: 30647838
Bosn J Basic Med Sci. 2019 Aug 20;19(3):227-233
pubmed: 30915922
Nat Rev Mol Cell Biol. 2001 Apr;2(4):285-93
pubmed: 11283726
Biochim Biophys Acta Rev Cancer. 2018 Aug;1870(1):51-66
pubmed: 29959989
Ann Oncol. 2015 Aug;26(8):1533-46
pubmed: 25939896
Clin Breast Cancer. 2018 Oct;18(5):e1111-e1116
pubmed: 30025999
Am J Pathol. 2004 Mar;164(3):903-14
pubmed: 14982844
Biochim Biophys Acta. 2011 Aug;1816(1):73-9
pubmed: 21515339
Curr Med Chem. 2012;19(35):6036-49
pubmed: 22963570
Am J Pathol. 2000 Nov;157(5):1523-35
pubmed: 11073812
J Cancer Res Clin Oncol. 2016 Jun;142(6):1261-71
pubmed: 27038158
BMC Cancer. 2018 Jun 19;18(1):669
pubmed: 29921237
Eur J Surg Oncol. 2017 Apr;43(4):642-648
pubmed: 27889196
Int J Oncol. 2013 Aug;43(2):365-74
pubmed: 23708710
Curr Treat Options Oncol. 2019 Mar 28;20(4):35
pubmed: 30923913
Cells. 2019 May 16;8(5):
pubmed: 31100966
Histol Histopathol. 2018 Feb;33(2):133-145
pubmed: 28681373
Am J Pathol. 2005 Mar;166(3):751-60
pubmed: 15743787
Expert Opin Pharmacother. 2015 May;16(7):983-98
pubmed: 25881743
Oncotarget. 2019 Mar 15;10(22):2189-2202
pubmed: 31040910
J Virol. 2015 May;89(9):4866-79
pubmed: 25673725
BMC Cancer. 2006 Jul 12;6:186
pubmed: 16836752
Expert Opin Ther Targets. 2012 Sep;16(9):881-7
pubmed: 22800288
Pathol Int. 2017 Aug;67(8):404-413
pubmed: 28699235
Cancer Res. 2017 Jan 15;77(2):545-556
pubmed: 27879270
Sci Rep. 2018 Oct 8;8(1):14951
pubmed: 30297706
Cancer Sci. 2020 May;111(5):1840-1850
pubmed: 32086991
JAMA Surg. 2014 Feb;149(2):125-9
pubmed: 24306257
Semin Cancer Biol. 2018 Oct;52(Pt 2):66-74
pubmed: 29574171