title: Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer.
abstract: There is accumulating evidence that the transforming growth factor beta (TGF-β) and nuclear factor kappa-B (NFκB) pathways are tightly connected and play a key role in malignant transformation in cancer. Immune infiltration by regulatory T- and B-lymphocytes (Tregs, Bregs) has recently gained increased attention for being an important source of TGF-β. There is a plethora of studies examining the pro-tumorigenic functions of carcinoembryonic antigen (CEA), but its receptor CEAR is far less studied. So far, there is a single connecting report that TGF-β also may signal through CEAR. The crosstalk between cancer tissues is further complicated by the expression of CEAR and TGF-β receptors in stromal cells, and implications of TGF-β in epithelial-mesenchymal transition. Furthermore, tumor-infiltrating Tregs and Bregs may directly instruct cancer cells by secreting TGF-β binding to their CEAR. Therefore, both TGF-β and CEA may act synergistically in breast cancer and cause disease progression, and NFκB could be a common crossing point between their signaling. CEAR, TGF-β1-3, TGF-β-R types I-III and NFκB class I and II molecules have an outstanding human-canine sequence identity, and only a canine CEA homolog has not yet been identified. For these reasons, the dog may be a valid translational model patient for investigating the crosstalk of the interconnected CEA and TGF-β networks.
authors.affiliation: Department of Comparative Medicine, Comparative Immunology and Oncology, Messerli Research Institute of the University of Veterinary Medicine Vienna, c/o Institute of Pathophysiology and Allergy Research, AKH 4Q, Medical University Vienna and University Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria, erika.jensen-jarolim@meduniwien.ac.at.
authors.forename: Erika
authors.initials: E
authors.lastname: Jensen-Jarolim
authors.forename: Judit
authors.initials: J
authors.lastname: Fazekas
authors.forename: Josef
authors.initials: J
authors.lastname: Singer
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Hofstetter
authors.forename: Kumiko
authors.initials: K
authors.lastname: Oida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuda
authors.forename: Akane
authors.initials: A
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000378:metabolism*; D004283:Dog Diseases / Q000276:immunology*; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000662:veterinary; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D002272:Carcinoembryonic Antigen; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C065686:carcinoembryonic antigen binding protein, human; D051550:I-kappa B Kinase
references.citation: Vet J. 2012 Jul;193(1):222-7
references.pmid: 22130461
references.citation: Cancer Immunol Immunother. 2014 Jan;63(1):67-72
references.pmid: 24213679
references.citation: J Clin Oncol. 2001 Mar 15;19(6):1865-78
references.pmid: 11251019
references.citation: Nature. 2005 Dec 8;438(7069):803-19
references.pmid: 16341006
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Cancer Microenviron. 2015 Dec;8(3):159-66
references.pmid: 25106539
references.citation: Cancer Res. 2008 Mar 1;68(5):1462-70
references.pmid: 18316610
references.citation: PLoS One. 2013 Sep 11;8(9):e74654
references.pmid: 24040308
references.citation: Nat Struct Biol. 2002 Mar;9(3):203-8
references.pmid: 11850637
references.citation: Methods Mol Biol. 2014;1190:271-89
references.pmid: 25015287
references.citation: Blood. 2005 May 15;105(10):3925-34
references.pmid: 15687237
references.citation: J Immunol. 2010 Apr 1;184(7):3897-906
references.pmid: 20200282
references.citation: J Clin Oncol. 2008 Aug 1;26(22):3681-6
references.pmid: 18669452
references.citation: Clin Exp Metastasis. 2011 Dec;28(8):923-32
references.pmid: 21901530
references.citation: J Clin Invest. 2013 Jan;123(1):150-63
references.pmid: 23241956
references.citation: Mol Immunol. 2012 Apr;50(4):200-9
references.pmid: 22424313
references.citation: Oncol Rep. 2013 Sep;30(3):1215-22
references.pmid: 23807713
references.citation: Zhonghua Wei Chang Wai Ke Za Zhi. 2010 Aug;13(8):608-11
references.pmid: 20737316
references.citation: Tumour Biol. 2014 Jan;35(1):379-85
references.pmid: 23918305
references.citation: Cancer Res. 2010 Oct 15;70(20):8159-68
references.pmid: 20889724
references.citation: Int J Cancer. 2014 Jun 1;134(11):2583-94
references.pmid: 24214914
references.citation: BMC Evol Biol. 2007 Oct 18;7:196
references.pmid: 17945019
references.citation: Blood. 2013 May 30;121(22):4493-503
references.pmid: 23603913
references.citation: Sci Rep. 2014 Feb 17;4:4057
references.pmid: 24531845
references.citation: J Vet Intern Med. 2009 Jul-Aug;23(4):875-81
references.pmid: 19496904
references.citation: J Biol Chem. 2001 Aug 17;276(33):31067-73
references.pmid: 11406629
references.citation: J Clin Oncol. 2005 Mar 20;23(9):2078-93
references.pmid: 15774796
references.citation: J Biol Chem. 2008 Jun 6;283(23):15647-55
references.pmid: 18375392
references.citation: Cell Death Differ. 2006 May;13(5):861-72
references.pmid: 16470223
references.citation: Biomed Res Int. 2014;2014:502093
references.pmid: 25089270
references.citation: Cancer Gene Ther. 2011 Dec;18(12):850-8
references.pmid: 21869824
references.citation: Anticancer Res. 2005 Jan-Feb;25(1A):23-31
references.pmid: 15816515
references.citation: Nat Immunol. 2011 Jul 19;12(8):695-708
references.pmid: 21772278
references.citation: Exp Cell Res. 2014 Jun 10;324(2):115-23
references.pmid: 24726916
references.citation: Cancer Immunol Immunother. 1998 Mar;46(1):14-20
references.pmid: 9520287
references.citation: Cancer Immunol Immunother. 2015 Feb;64(2):137-48
references.pmid: 25548094
references.citation: Front Immunol. 2013 Jul 11;4:190
references.pmid: 23874336
references.citation: Prev Vet Med. 2005 Jun 10;69(1-2):109-27
references.pmid: 15899300
references.citation: Cancer Res. 2013 Apr 15;73(8):2468-79
references.pmid: 23384943
references.citation: Exp Cell Res. 2008 Sep 10;314(15):2725-38
references.pmid: 18586026
references.citation: Cancer Cell. 2012 Nov 13;22(5):571-84
references.pmid: 23153532
references.citation: Oncogene. 2013 Mar 21;32(12):1549-59
references.pmid: 22641218
references.citation: Cancer Res. 2011 May 15;71(10):3505-15
references.pmid: 21444674
references.citation: Cancer Growth Metastasis. 2014 Mar 23;7:1-8
references.pmid: 24741325
references.citation: Int J Cancer. 1996 Nov 15;68(4):457-63
references.pmid: 8945616
references.citation: Cell Cycle. 2010 Nov 15;9(22):4461-8
references.pmid: 21088486
references.citation: Mol Cancer Ther. 2014 Jul;13(7):1777-1790
references.pmid: 24755200
references.citation: Oncogene. 2010 Aug 26;29(34):4741-51
references.pmid: 20531305
references.citation: Nat Methods. 2010 Mar;7(3):167-8
references.pmid: 20195246
references.citation: Biomed Res Int. 2014;2014:130894
references.pmid: 24672781
references.citation: Curr Opin Genet Dev. 2008 Feb;18(1):19-26
references.pmid: 18440219
references.citation: PLoS One. 2014 Aug 13;9(8):e105027
references.pmid: 25119018
references.citation: Cancer Immunol Immunother. 2011 Aug;60(8):1181-93
references.pmid: 21688178
references.citation: Front Genet. 2013 Apr 08;4:46
references.pmid: 23579348
references.citation: Cell. 1992 Dec 11;71(6):1003-14
references.pmid: 1333888
references.citation: EMBO J. 2011 Apr 6;30(7):1263-76
references.pmid: 21423151
references.citation: Genomics. 2005 Nov;86(5):566-80
references.pmid: 16139472
references.citation: J Immunother. 2009 Jan;32(1):12-21
references.pmid: 19307989
references.citation: PLoS Curr. 2011 Mar 16;3:RRN1223
references.pmid: 21436956
references.citation: J Pept Sci. 2012 Apr;18(4):252-60
references.pmid: 22392880
references.citation: Oncogene. 2008 Jan 24;27(5):675-83
references.pmid: 17653079
references.citation: J Natl Cancer Inst. 1990 Mar 7;82(5):380-5
references.pmid: 2304087
references.citation: Immunity. 2012 Nov 16;37(5):930-46
references.pmid: 23123061