title: Growth, metastasis, and expression of CCL2 and CCL5 by murine mammary carcinomas are dependent upon Myd88.
abstract: Previously we reported that lipopolysaccharide (LPS) treatment of murine mammary carcinomas resulted in decreased growth of the tumors. Here we show the decreased growth following LPS treatment was mediated through effects downstream of TLR4 and Myd88. Perhaps more notably, simply reducing TLR4 or Myd88 levels was sufficient to slow tumor growth rates. Moreover, reduced levels of Myd88 correlated with a significant reduction in lung metastasis as well as decreased CCL2 and CCL5 expression. To determine whether inhibiting Myd88 function could also alter tumor growth and chemokine expression we used a Myd88 homodimerization inhibitory peptide. Indeed, inhibiting Myd88 function in four different murine mammary carcinomas as well as the human breast cancer cell line MDA-MB-231 led to decreased growth as well as CCL2 and CCL5 expression. These data imply that Myd88 is important for growth and metastasis of breast cancer, and expression of at least two proinflammatory chemokines.
authors.affiliation: Department of Biology, Lafayette College, Easton, PA 18042, USA.
authors.forename: Adetutu T
authors.initials: AT
authors.lastname: Egunsola
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Zawislak
authors.forename: Afua A
authors.initials: AA
authors.lastname: Akuffo
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Chalmers
authors.forename: Jason C
authors.initials: JC
authors.lastname: Ewer
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Vail
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lombardo
authors.forename: Dana N
authors.initials: DN
authors.lastname: Perez
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kurt
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009362:Neoplasm Metastasis; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; D018932:Chemokine CCL2; D018946:Chemokine CCL5; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4
references.citation: Cell Mol Life Sci. 2010 Dec;67(24):4109-34
references.pmid: 20680392
references.citation: PLoS One. 2010 Nov 05;5(11):e13859
references.pmid: 21079774
references.citation: J Exp Clin Cancer Res. 2010 Jul 10;29:92
references.pmid: 20618976
references.citation: Nature. 2011 Feb 3;470(7332):115-9
references.pmid: 21179087
references.citation: Clin Cancer Res. 2000 Aug;6(8):3282-9
references.pmid: 10955814
references.citation: J Clin Invest. 2010 Oct;120(10):3663-7
references.pmid: 20941850
references.citation: Cancer Res. 2011 Aug 15;71(16):5467-76
references.pmid: 21730023
references.citation: Cancer Res. 2006 May 15;66(10):5427-35
references.pmid: 16707471
references.citation: Cancer Biol Ther. 2011 Jan 1;11(1):58-67
references.pmid: 21248470
references.citation: Cancer Res. 1999 Sep 15;59(18):4681-7
references.pmid: 10493525
references.citation: Cell Immunol. 2010;266(1):67-75
references.pmid: 20869044
references.citation: J Mol Med (Berl). 2011 Feb;89(2):123-36
references.pmid: 20865400
references.citation: Cancer Res. 2005 Jun 15;65(12):5009-14
references.pmid: 15958541
references.citation: J Immunol. 2011 Sep 1;187(5):2775-82
references.pmid: 21804019
references.citation: J Immunol. 2006 Jun 1;176(11):6624-30
references.pmid: 16709820
references.citation: Cancer Res. 2008 Jun 1;68(11):4026-30
references.pmid: 18519658
references.citation: Int J Biol Sci. 2010 Nov 03;6(7):675-81
references.pmid: 21060729
references.citation: Cancer Res. 2007 May 1;67(9):4346-52
references.pmid: 17483348
references.citation: J Leukoc Biol. 2007 Oct;82(4):801-10
references.pmid: 17548806
references.citation: Clin Cancer Res. 2001 Feb;7(2):285-9
references.pmid: 11234881
references.citation: Science. 2007 Jul 6;317(5834):124-7
references.pmid: 17615359
references.citation: Future Oncol. 2011 Feb;7(2):309-20
references.pmid: 21345147
references.citation: Cancer Res. 1999 Sep 1;59(17):4325-33
references.pmid: 10485480
references.citation: Immunol Invest. 2009;38(8):730-48
references.pmid: 19860585
references.citation: Shock. 2006 Aug;26(2):174-9
references.pmid: 16878026
references.citation: Cancer. 2001 Sep 1;92(5):1085-91
references.pmid: 11571719
references.citation: J Immunol. 2011 Feb 15;186(4):1963-9
references.pmid: 21217015
references.citation: Tumour Biol. 2004 Jan-Apr;25(1-2):14-7
references.pmid: 15192307
references.citation: Science. 2007 Jul 6;317(5834):121-4
references.pmid: 17615358
references.citation: J Proteome Res. 2008 Sep;7(9):3830-7
references.pmid: 18683965