title: Lack of functional TSLP receptors mitigates Th2 polarization and the establishment and growth of 4T1 primary breast tumours but has different effects on tumour quantities in the lung and brain.
abstract: The 4T1 mammary carcinoma cell line produces TSLP. We had hypothesized that TSLP promotes the development of a permissive environment for the growth and metastasis of primary tumour and that this is associated with a Th2-polarized antitumour immune response. We found that, in Tslpr(-/-) mice, the mean tumour diameters were smaller from days 27 to 40, and relatively fewer tumour cells were present in the lung, compared with wild-type mice. Polarization of the Th2 cytokine profile was also diminished in Tslpr(-/-) mice. These findings confirmed those reported previously by others. Here, we further show that primary tumours are established less often in Tslpr(-/-) mice and that, unexpectedly, the relative number of tumour cells in the brain is greater in Tslpr(-/-) mice compared with wild-type mice. Findings from our cytotoxicity assays show that 4T1-directed lysis is undetectable in both WT and Tslpr(-/-) mice, ruling out the possibility that altered cytotoxic responses in Tslpr(-/-) mice are responsible for the differences we observed. In a human tissue microarray, positive staining for TSLP was seen in tumour cells from breast cancer tissue, but it was also seen in normal glandular epithelial cells from normal breast tissue, which has not been shown before. Thus, our findings provide new insight into the effects of TSLP in metastatic breast cancer.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: R B
authors.initials: RB
authors.lastname: Erdmann
authors.forename: J G
authors.initials: JG
authors.lastname: Gartner
authors.forename: W J
authors.initials: WJ
authors.lastname: Leonard
authors.forename: C A
authors.initials: CA
authors.lastname: Ellison
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000172:deficiency / Q000235:genetics*; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D018121:Receptors, Cytokine; C410591:Tslpr protein, mouse
references.citation: J Exp Med. 2000 Sep 4;192(5):659-70
references.pmid: 10974032
references.citation: J Allergy Clin Immunol. 2008 Dec;122(6):1208-14
references.pmid: 18926564
references.citation: Breast. 2007 Dec;16 Suppl 2:S27-33
references.pmid: 17764938
references.citation: BMC Cancer. 2008 Aug 09;8:228
references.pmid: 18691423
references.citation: J Immunol Methods. 1984 Mar 30;68(1-2):235-49
references.pmid: 6200539
references.citation: Nat Immunol. 2003 Aug;4(8):773-9
references.pmid: 12872121
references.citation: Exp Hematol. 1994 Mar;22(3):321-8
references.pmid: 8112430
references.citation: J Immunol. 2008 Nov 1;181(9):6557-62
references.pmid: 18941246
references.citation: Nat Immunol. 2002 Jul;3(7):673-80
references.pmid: 12055625
references.citation: J Immunol. 2007 Jun 1;178(11):6720-4
references.pmid: 17513717
references.citation: J Immunol. 2011 May 15;186(10):5656-62
references.pmid: 21490155
references.citation: J Immunol. 2012 Sep 15;189(6):3130-9
references.pmid: 22896632
references.citation: Cancer Res. 1998 Apr 1;58(7):1486-93
references.pmid: 9537252
references.citation: Mult Scler. 2003 Dec;9(6):540-9
references.pmid: 14664465
references.citation: Nat Immunol. 2010 Apr;11(4):289-93
references.pmid: 20300138
references.citation: J Clin Immunol. 1981 Jan;1(1):51-63
references.pmid: 7334070
references.citation: J Immunol. 2001 Jul 1;167(1):336-43
references.pmid: 11418668
references.citation: Curr Protoc Immunol. 2001 May;Chapter 20:Unit 20.2
references.pmid: 18432775
references.citation: Br J Cancer. 2006 Sep 4;95(5):616-26
references.pmid: 16880783
references.citation: J Immunol. 2008 Dec 1;181(11):7699-705
references.pmid: 19017958
references.citation: Hum Gene Ther. 1993 Aug;4(4):419-31
references.pmid: 8399489
references.citation: Clin Immunol. 2008 Nov;129(2):202-10
references.pmid: 18757241
references.citation: J Exp Med. 2004 Jul 19;200(2):159-68
references.pmid: 15263024
references.citation: Am J Pathol. 2001 Dec;159(6):2355-69
references.pmid: 11733384
references.citation: Eur J Immunol. 2008 Jun;38(6):1487-92
references.pmid: 18461563
references.citation: J Immunol. 1995 Nov 1;155(9):4189-98
references.pmid: 7594574
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11070-5
references.pmid: 15263090
references.citation: J Exp Med. 2005 Nov 7;202(9):1213-23
references.pmid: 16275760
references.citation: Annu Rev Immunol. 2007;25:193-219
references.pmid: 17129180
references.citation: Nat Immunol. 2000 Jul;1(1):59-64
references.pmid: 10881176
references.citation: Lancet. 2008 Mar 1;371(9614):771-83
references.pmid: 18275997
references.citation: Nature. 2002 Dec 19-26;420(6917):860-7
references.pmid: 12490959
references.citation: Breast Cancer Res. 2007;9(4):212
references.pmid: 17705880
references.citation: Nat Immunol. 2005 Oct;6(10):1047-53
references.pmid: 16142237
references.citation: Trends Immunol. 2007 Jan;28(1):12-8
references.pmid: 17129764
references.citation: Exp Neurol. 2004 Dec;190(2):446-55
references.pmid: 15530883
references.citation: J Immunol. 2008 Sep 15;181(6):4311-9
references.pmid: 18768889
references.citation: J Immunol. 1999 Jan 15;162(2):677-83
references.pmid: 9916685
references.citation: J Immunol. 2007 Feb 1;178(3):1396-404
references.pmid: 17237387
references.citation: Microbes Infect. 2011 Sep;13(10):828-36
references.pmid: 21609776
references.citation: J Exp Med. 2005 Sep 19;202(6):829-39
references.pmid: 16172260
references.citation: J Exp Med. 2005 Aug 15;202(4):541-9
references.pmid: 16103410
references.citation: CMAJ. 1996 Aug 1;155(3):281-3
references.pmid: 8705906
references.citation: Blood. 2004 Feb 1;103(3):843-51
references.pmid: 14512322
references.citation: J Exp Med. 2011 Mar 14;208(3):479-90
references.pmid: 21339324
references.citation: J Immunol. 2005 Jun 15;174(12):8183-90
references.pmid: 15944327