title: Recruitment of mesenchymal stem cells into prostate tumours promotes metastasis.
abstract: Tumours recruit mesenchymal stem cells to facilitate healing, which induces their conversion into cancer-associated fibroblasts that facilitate metastasis. However, this process is poorly understood on the molecular level. Here we show that CXCL16, a ligand for CXCR6, facilitates mesenchymal stem cell or very small embryonic-like cells recruitment into prostate tumours. CXCR6 signalling stimulates the conversion of mesenchymal stem cells into cancer-associated fibroblasts, which secrete stromal-derived factor-1, also known as CXCL12. CXCL12 expressed by cancer-associated fibroblasts then binds to CXCR4 on tumour cells and induces an epithelial-to-mesenchymal transition, which ultimately promotes metastasis to secondary tumour sites. Our results provide the molecular basis for mesenchymal stem cell recruitment into tumours and how this process leads to tumour metastasis.
authors: Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109, USA.
authors: Younghun
authors: Y
authors: Jung
authors: Jin Koo
authors: JK
authors: Kim
authors: Yusuke
authors: Y
authors: Shiozawa
authors: Jingcheng
authors: J
authors: Wang
authors: Anjali
authors: A
authors: Mishra
authors: Jeena
authors: J
authors: Joseph
authors: Janice E
authors: JE
authors: Berry
authors: Samantha
authors: S
authors: McGee
authors: Eunsohl
authors: E
authors: Lee
authors: Hongli
authors: H
authors: Sun
authors: Jianhua
authors: J
authors: Wang
authors: Taocong
authors: T
authors: Jin
authors: Honglai
authors: H
authors: Zhang
authors: Jinlu
authors: J
authors: Dai
authors: Paul H
authors: PH
authors: Krebsbach
authors: Evan T
authors: ET
authors: Keller
authors: Kenneth J
authors: KJ
authors: Pienta
authors: Russell S
authors: RS
authors: Taichman
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000378:metabolism; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D054387:Receptors, CXCR / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000378:metabolism; D051116:Receptors, Scavenger / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C423727:CXCL16 protein, human; C106330:CXCR6 protein, human; D054377:Chemokine CXCL12; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; C498926:Cxcl16 protein, mouse; C482906:Cxcr6 protein, mouse; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D051116:Receptors, Scavenger; D011991:Receptors, Virus
references: Cell. 2005 Dec 16;123(6):1001-11
references: 16360031
references: Cancer Cell. 2007 Jan;11(1):3-5
references: 17222787
references: N Engl J Med. 1986 Dec 25;315(26):1650-9
references: 3537791
references: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references: 22237781
references: J Immunol. 2003 Feb 1;170(3):1136-40
references: 12538668
references: Blood. 2001 May 15;97(10):3283-91
references: 11342460
references: Science. 1999 Feb 5;283(5403):845-8
references: 9933168
references: J Leukoc Biol. 2010 Jun;87(6):1029-39
references: 20181724
references: PLoS One. 2009 Aug 19;4(8):e6695
references: 19690611
references: J Immunol. 2007 Dec 15;179(12):8172-9
references: 18056360
references: Nat Immunol. 2000 Oct;1(4):298-304
references: 11017100
references: Genes Dev. 2008 Mar 1;22(5):559-74
references: 18316475
references: Cancer Cell. 2011 Feb 15;19(2):257-72
references: 21316604
references: Nature. 2001 Mar 1;410(6824):50-6
references: 11242036
references: J Biol Chem. 2008 Feb 15;283(7):4283-94
references: 18057003
references: Int J Oncol. 2008 Aug;33(2):297-308
references: 18636150
references: Glia. 2008 May;56(7):764-74
references: 18293410
references: Cancer Res. 2010 Jan 15;70(2):471-80
references: 20068185
references: Stem Cell Rev. 2008 Summer;4(2):89-99
references: 18459073
references: Cancer Sci. 2008 Jul;99(7):1362-9
references: 18452560
references: Exp Cell Res. 2001 Mar 10;264(1):169-84
references: 11237532
references: Aging Cell. 2005 Dec;4(6):291-8
references: 16300481
references: Clin Transl Oncol. 2011 Sep;13(9):611-6
references: 21865132
references: Lung Cancer. 2004 Aug;45 Suppl 2:S163-75
references: 15552797
references: J Biol Chem. 2004 Jan 30;279(5):3188-96
references: 14625285
references: Cancer Metastasis Rev. 2010 Jun;29(2):249-61
references: 20411303
references: Stem Cells. 2006 Jun;24(6):1573-82
references: 16769762
references: Cancer Res. 2008 Dec 15;68(24):10367-76
references: 19074906
references: Mol Med Rep. 2011 May-Jun;4(3):419-24
references: 21468586
references: Cancer Res. 2008 Jun 15;68(12):4701-8
references: 18559516
references: Nat Cell Biol. 2006 Dec;8(12):1321-3
references: 17139281
references: Mol Cancer Res. 2008 Apr;6(4):546-54
references: 18344492
references: J Immunol. 2001 Apr 15;166(8):5145-54
references: 11290797
references: Blood. 2005 Sep 15;106(6):1901-10
references: 15890683
references: Cancer Metastasis Rev. 2006 Dec;25(4):573-87
references: 17165132
references: Oncogene. 2008 Oct 6;27(45):5904-12
references: 18836471
references: Cell Cycle. 2006 Aug;5(15):1597-601
references: 16880743
references: Cancer Res. 2002 Mar 15;62(6):1832-7
references: 11912162
references: Ann Surg Oncol. 2012 Jul;19 Suppl 3:S518-27
references: 21845497
references: Nature. 2007 Oct 4;449(7162):557-63
references: 17914389
references: Nature. 2005 Dec 8;438(7069):820-7
references: 16341007
references: Proc Natl Acad Sci U S A. 1971 Apr;68(4):820-3
references: 5279523
references: Carcinogenesis. 2011 Apr;32(4):477-87
references: 21252118
references: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3806-11
references: 19234121
references: Stem Cells Dev. 2010 Oct;19(10):1557-70
references: 20446812
references: Am J Pathol. 1999 Sep;155(3):787-98
references: 10487836
references: Nature. 2010 Apr 8;464(7290):852-7
references: 20305640
references: Cancer Res. 2009 Feb 15;69(4):1255-8
references: 19208837
references: Arch Ital Urol Androl. 2006 Dec;78(4):130-4
references: 17269615
references: Biochim Biophys Acta. 2010 Aug;1806(1):42-9
references: 20122997
references: Nat Med. 2008 Feb;14(2):181-7
references: 18193058
references: J Biol Chem. 2011 Jul 15;286(28):25007-15
references: 21592963
references: Hum Pathol. 2001 Jul;32(7):690-7
references: 11486167
references: Oncogene. 2004 Sep 23;23(44):7366-77
references: 15326482