title: Cancer to bone: a fatal attraction.
abstract: When cancer metastasizes to bone, considerable pain and deregulated bone remodelling occurs, greatly diminishing the possibility of cure. Metastasizing tumour cells mobilize and sculpt the bone microenvironment to enhance tumour growth and to promote bone invasion. Understanding the crucial components of the bone microenvironment that influence tumour localization, along with the tumour-derived factors that modulate cellular and protein matrix components of bone to favour tumour expansion and invasion, is central to the pathophysiology of bone metastases. Basic findings of tumour-bone interactions have uncovered numerous therapeutic opportunities that focus on the bone microenvironment to prevent and treat bone metastases.
authors: Department of Medicine, Division of Molecular Oncology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. kweilbae@wustl.edu
authors: Katherine N
authors: KN
authors: Weilbaecher
authors: Theresa A
authors: TA
authors: Guise
authors: Laurie K
authors: LK
authors: McCauley
references: Nat Rev Rheumatol. 2009 Dec;5(12):667-76
references: 19884898
references: Blood. 2005 Dec 15;106(13):4294-302
references: 16118323
references: Nature. 2003 Oct 23;425(6960):841-6
references: 14574413
references: J Cell Biochem. 2010 Apr 1;109(5):927-32
references: 20052668
references: Curr Pharm Des. 2003;9(32):2643-58
references: 14529538
references: Leuk Lymphoma. 1994 Jun;14(1-2):19-28
references: 7522718
references: N Engl J Med. 2003 Dec 25;349(26):2483-94
references: 14695408
references: Proc Natl Acad Sci U S A. 2008 May 6;105(18):6620-5
references: 18443294
references: Br J Cancer. 2007 Oct 8;97(7):964-70
references: 17876334
references: Ann N Y Acad Sci. 2007 Nov;1116:392-413
references: 18083941
references: Arterioscler Thromb Vasc Biol. 2008 Oct;28(10):1703-13
references: 18658045
references: Nat Med. 2007 Jan;13(1):62-9
references: 17159986
references: Bone. 2009 May;44(5):908-16
references: 19442620
references: Cancer Res. 2004 Jul 1;64(13):4514-22
references: 15231661
references: PLoS One. 2009;4(4):e5275
references: 19357790
references: Nat Med. 1995 Sep;1(9):944-9
references: 7585222
references: Clin Exp Metastasis. 1997 May;15(3):218-27
references: 9174123
references: Br J Urol. 1991 Jul;68(1):74-80
references: 1873694
references: Eur J Gastroenterol Hepatol. 2001 Sep;13(9):1083-8
references: 11564960
references: Nat Rev Cancer. 2010 Jun;10(6):415-24
references: 20495575
references: Cell. 2008 Jun 13;133(6):994-1005
references: 18555776
references: N Engl J Med. 2000 Feb 24;342(8):525-33
references: 10684910
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6213s-6216s
references: 17062703
references: Int J Cancer. 2006 Feb 15;118(4):850-6
references: 16108038
references: Breast Cancer Res Treat. 2007 Sep;105(1):95-104
references: 17136477
references: Cancer Res. 2005 Jul 1;65(13):5778-84
references: 15994953
references: J Natl Cancer Inst. 1970 Oct;45(4):773-82
references: 5513503
references: PLoS One. 2009 Sep 03;4(9):e6896
references: 19727403
references: J Exp Med. 2006 Nov 27;203(12):2673-82
references: 17088434
references: Cancer Res. 2006 Sep 1;66(17):8648-54
references: 16951179
references: Blood. 1999 Dec 1;94(11):3883-8
references: 10572104
references: Nature. 2008 Dec 11;456(7223):814-8
references: 18997773
references: J Cell Biochem. 2008 Jul 1;104(4):1311-23
references: 18260128
references: Nat Rev Cancer. 2011 Feb;11(2):123-34
references: 21258396
references: Cancer Res. 2004 Dec 1;64(23):8604-12
references: 15574767
references: Cell. 2005 May 6;121(3):335-48
references: 15882617
references: Cancer Res. 1991 Jul 15;51(14):3753-61
references: 1712249
references: Cancer Res. 2010 Mar 1;70(5):1835-44
references: 20160035
references: Eur J Cancer. 2011 Jan;47(2):277-86
references: 20863686
references: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14205-10
references: 14612570
references: Science. 2008 Jan 11;319(5860):195-8
references: 18187653
references: Clin Exp Metastasis. 2004;21(1):19-29
references: 15065599
references: N Engl J Med. 2004 Apr 15;350(16):1655-64
references: 15084698
references: J Clin Oncol. 2010 Dec 10;28(35):5132-9
references: 21060033
references: Blood. 2001 Dec 15;98(13):3534-40
references: 11739154
references: Cancer Invest. 2008 Feb;26(1):53-9
references: 18181046
references: Oncology. 2009;77(2):92-9
references: 19590249
references: Curr Mol Med. 2010 Feb;10(1):71-81
references: 20205680
references: Cancer Res. 2010 Sep 15;70(18):7273-82
references: 20807818
references: Blood. 2010 Jun 3;115(22):4605-13
references: 20086246
references: Cell. 2004 Apr 30;117(3):387-98
references: 15109498
references: Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3897-902
references: 18322009
references: J Orthop Sci. 2000;5(1):75-81
references: 10664443
references: Semin Radiat Oncol. 2000 Apr;10(2):103-14
references: 10727599
references: Cancer Cell. 2009 Jul 7;16(1):67-78
references: 19573813
references: Cancer Cell. 2011 Feb 15;19(2):192-205
references: 21295524
references: Neoplasia. 2008 Aug;10(8):797-803
references: 18670640
references: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18813-8
references: 16354837
references: Nat Rev Cancer. 2008 May;8(5):377-86
references: 18385683
references: Nat Rev Cancer. 2008 Mar;8(3):212-26
references: 18292776
references: J Urol. 2008 Sep;180(3):1154-60
references: 18639279
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6231s-6235s
references: 17062706
references: Nature. 2010 Aug 12;466(7308):829-34
references: 20703299
references: J Natl Cancer Inst. 2004 Nov 3;96(21):1593-603
references: 15523088
references: Cancer Cell. 2008 Sep 9;14(3):201-11
references: 18772110
references: J Clin Oncol. 2005 Aug 1;23(22):4925-35
references: 15983391
references: Nat Rev Immunol. 2006 Nov;6(11):836-48
references: 17063185
references: Nature. 2010 Apr 15;464(7291):999-1005
references: 20393555
references: Mol Cancer. 2007 Mar 07;6:18
references: 17343740
references: Clin Cancer Res. 2008 Oct 15;14(20):6387-95
references: 18927277
references: J Clin Invest. 1999 Jan;103(2):197-206
references: 9916131
references: Anticancer Res. 2005 Jan-Feb;25(1A):79-83
references: 15816522
references: Br J Haematol. 2010 Mar;148(5):805-7
references: 19958354
references: Nature. 2003 Oct 23;425(6960):836-41
references: 14574412
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6309s-6314s
references: 17062720
references: J Cell Biochem. 2006 Mar 1;97(4):661-72
references: 16447163
references: Nat Med. 2009 Jul;15(7):757-65
references: 19584867
references: Prostate. 2011 Feb 15;71(3):268-80
references: 20717904
references: Eur J Cancer. 2010 May;46(7):1232-40
references: 20307969
references: J Clin Invest. 2004 Dec;114(12):1714-25
references: 15599396
references: Clin Cancer Res. 2007 Sep 1;13(17):5001-9
references: 17785550
references: J Pathol. 2007 Jan;211(1):10-7
references: 17083146
references: Anticancer Agents Med Chem. 2008 Apr;8(3):342-9
references: 18393792
references: Cancer Res. 2007 Sep 15;67(18):8742-51
references: 17875715
references: PLoS One. 2010 Aug 16;5(8):e12180
references: 20808935
references: J Pathol. 2002 Mar;196(3):254-65
references: 11857487
references: Cancer Res. 2008 Jul 15;68(14):5785-94
references: 18632632
references: Breast Cancer Res. 2010;12(5):R89
references: 21029421
references: Prostate. 2007 Jan 1;67(1):61-73
references: 17034033
references: Cancer Res. 2010 May 1;70(9):3494-504
references: 20406980
references: Endocrinology. 2005 Apr;146(4):1727-36
references: 15637291
references: Blood. 2004 Aug 15;104(4):993-1001
references: 15100152
references: Endocrinology. 2000 Dec;141(12):4357-64
references: 11108243
references: Prostate. 2006 Jan 1;66(1):32-48
references: 16114056
references: Cancer Res. 2006 Aug 1;66(15):7548-53
references: 16885353
references: J Biol Chem. 2005 Sep 2;280(35):30689-96
references: 16000305
references: Cell Res. 2008 Aug;18(8):858-70
references: 18645583
references: Nature. 2005 Dec 8;438(7069):820-7
references: 16341007
references: J Bone Miner Res. 2001 Apr;16(4):652-9
references: 11315992
references: Nat Rev Genet. 2003 Aug;4(8):638-49
references: 12897775
references: Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1454-9
references: 15665096
references: Cancer Res. 2009 Feb 1;69(3):1230-9
references: 19155301
references: Semin Hematol. 2000 Jan;37(1 Suppl 2):11-8
references: 10718154
references: Hum Gene Ther. 2010 Sep;21(9):1057-66
references: 20649485
references: Blood. 2007 Apr 15;109(8):3424-31
references: 17192391
references: Bone. 2011 Jan;48(1):54-65
references: 20850578
references: Prostate. 1999 Jun 1;39(4):246-61
references: 10344214
references: Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6296s-6300s
references: 17062717
references: Am J Pathol. 2007 Sep;171(3):1047-57
references: 17724140
references: Neoplasia. 2010 Feb;12(2):116-27
references: 20126470
references: Cancer. 2008 Jul 1;113(1):193-201
references: 18459173
references: N Engl J Med. 2009 Feb 12;360(7):679-91
references: 19213681
references: Cancer Res. 2006 Feb 15;66(4):2250-6
references: 16489028
references: Clin Exp Metastasis. 1998 May;16(4):299-312
references: 9626809
references: Lab Invest. 2007 Nov;87(11):1077-91
references: 17724448
references: J Pathol. 2010 May;221(1):77-86
references: 20191615
references: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14062-7
references: 17715292
references: Cancer Res. 2007 Aug 15;67(16):7665-74
references: 17702698
references: J Bone Miner Res. 2011 Feb;26(2):229-38
references: 21254230
references: Cancer. 2003 Feb 1;97(3 Suppl):739-47
references: 12548571
references: J Bone Miner Res. 2011 Jan;26(1):125-34
references: 20684002
references: Cancer Treat Rev. 2001 Jun;27(3):165-76
references: 11417967
references: Prostate. 2010 Nov 1;70(15):1709-15
references: 20564322
references: Clin Cancer Res. 2003 Dec 15;9(17):6326-34
references: 14695131
references: Int J Cancer. 1995 Jan 27;60(3):300-7
references: 7829234
references: Blood. 1999 Mar 1;93(5):1658-67
references: 10029595
references: Am J Pathol. 1998 Sep;153(3):865-73
references: 9736035
references: Blood. 2005 Nov 1;106(9):3160-5
references: 16030194
references: Cancer Cell. 2005 May;7(5):485-96
references: 15894268
references: Trends Cell Biol. 2005 Apr;15(4):188-93
references: 15817374
references: Blood. 2009 Apr 30;113(18):4341-51
references: 19139079
references: Am J Physiol Cell Physiol. 2001 Feb;280(2):C382-93
references: 11208534
references: Oncogene. 2010 Feb 11;29(6):811-21
references: 19915614
references: Cancer Res. 2009 Sep 1;69(17):6807-14
references: 19690135
references: Bone. 2006 Nov;39(5):985-990
references: 16870519
references: Int J Cancer. 2011 Jan 15;128(2):352-60
references: 20715172
references: Nat Rev Cancer. 2010 Jan;10(1):9-22
references: 20029421
references: J Clin Endocrinol Metab. 2010 Oct;95(10):E229-33
references: 20668040
references: Cell. 2002 Jan 11;108(1):17-29
references: 11792318
references: J Natl Cancer Inst. 1998 Jan 21;90(2):118-23
references: 9450571
references: Expert Opin Investig Drugs. 2010 Jul;19(7):899-908
references: 20497097
references: J Biol Chem. 2003 Nov 14;278(46):45826-32
references: 12954626
references: J Cell Biochem. 2003 Jun 1;89(3):462-73
references: 12761880
references: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10954-9
references: 12941866
references: Anticancer Res. 2010 May;30(5):1807-13
references: 20592383
references: Stem Cells. 2004;22(7):1128-33
references: 15579633
references: J Exp Med. 2005 Jun 6;201(11):1781-91
references: 15928197
references: J Bone Miner Res. 2001 Sep;16(9):1575-82
references: 11547826
references: Nat Med. 2006 Jun;12(6):657-64
references: 16715089
references: J Biol Chem. 2008 Sep 5;283(36):24435-47
references: 18621740
references: ANZ J Surg. 2007 Aug;77(8):626-31
references: 17635273
references: Blood. 2000 Sep 1;96(5):1953-60
references: 10961900
references: Biochim Biophys Acta. 2006 Aug;1766(1):159-66
references: 16857321
references: Cancer Res. 2011 Jan 1;71(1):164-74
references: 21097719
references: Cancer Cell. 2003 Jun;3(6):537-49
references: 12842083
references: Cancer Res. 2007 May 1;67(9):4157-63
references: 17483326
references: Clin Breast Cancer. 2010 Dec 1;10(6):452-8
references: 21147688
references: Prostate. 2003 Jun 15;56(1):13-22
references: 12746842
references: Blood. 2004 Oct 1;104(7):2149-54
references: 15138161
references: J Bone Miner Res. 2010 Nov;25(11):2419-26
references: 20499365
references: J Natl Cancer Inst. 2010 Aug 4;102(15):1148-59
references: 20660365
references: Nature. 2010 Nov 4;468(7320):103-7
references: 20881963
references: J Natl Cancer Inst. 1996 Nov 20;88(22):1652-8
references: 8931609
references: Blood. 2009 Jun 11;113(24):6206-14
references: 19050309
references: Lancet Oncol. 2010 May;11(5):421-8
references: 20362507
references: Cell. 1997 May 30;89(5):755-64
references: 9182763
references: Mol Cancer Ther. 2007 Oct;6(10):2609-17
references: 17938257
references: Genes Dev. 2009 Aug 15;23(16):1882-94
references: 19608765
references: Blood. 2004 Apr 15;103(8):2942-9
references: 15070669
references: J Leukoc Biol. 2006 Dec;80(6):1183-96
references: 16997855
references: J Cell Mol Med. 2010 Aug;14(8):2037-44
references: 20597997
references: Nat Rev Cancer. 2002 Aug;2(8):584-93
references: 12154351
references: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13909-14
references: 16172383
references: J Clin Invest. 2011 Apr;121(4):1298-312
references: 21436587
references: J Bone Miner Res. 2010 Aug;25(8):1701-6
references: 20572008
references: Cancer Gene Ther. 2005 Jan;12(1):84-9
references: 15472715
references: J Bone Miner Res. 2005 Feb;20(2):318-29
references: 15647826
references: Am J Pathol. 1996 Jan;148(1):55-61
references: 8546226
references: J Clin Invest. 1996 Oct 1;98(7):1544-9
references: 8833902
references: Pain. 2001 Sep;93(3):247-257
references: 11514084
references: Bone. 2008 Dec;43(6):976-82
references: 18835590
references: J Clin Invest. 1989 Jul;84(1):43-50
references: 2786890
references: Mol Endocrinol. 2007 Feb;21(2):486-98
references: 17068196
references: Clin Exp Metastasis. 2003;20(5):437-44
references: 14524533
references: Nat Med. 2000 May;6(5):521-8
references: 10802707
references: Cancer Res. 2006 Sep 15;66(18):9065-73
references: 16982748
references: Nature. 2001 Mar 1;410(6824):50-6
references: 11242036
references: Nat Cell Biol. 2008 Nov;10(11):1349-55
references: 18820689
references: Blood. 2009 Aug 13;114(7):1331-9
references: 19141863
references: J Clin Oncol. 2000 Jan;18(1):80-6
references: 10623696
references: Blood. 2004 Oct 15;104(8):2484-91
references: 15187021
references: J Bone Miner Res. 2010 Jun;25(6):1295-304
references: 20200931
references: Clin Cancer Res. 2009 Jan 15;15(2):677-83
references: 19147774
references: Curr Cancer Drug Targets. 2009 Nov;9(7):801-6
references: 20025568
references: J Clin Oncol. 2009 Apr 1;27(10):1564-71
references: 19237632
references: Cancer Res. 2007 Mar 1;67(5):2317-24
references: 17332363
references: Exp Cell Res. 2009 Jul 15;315(12):2072-80
references: 19285978
references: Nat Med. 2009 Aug;15(8):960-6
references: 19597504
references: Cancer Res. 2007 Jan 1;67(1):425; author reply 426
references: 17210725
references: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9385-90
references: 19458257
references: Cancer Res. 2009 Feb 15;69(4):1685-92
references: 19176388
references: Endocr Rev. 1999 Jun;20(3):345-57
references: 10368775
references: J Bone Miner Res. 2010 Mar;25(3):440-6
references: 19653815
references: Cancer Res. 2007 Dec 1;67(23):11438-46
references: 18056472
references: Cancer Res. 2008 Nov 1;68(21):9050-9
references: 18974151
references: Genes Dev. 1999 Sep 15;13(18):2412-24
references: 10500098
references: Exp Cell Res. 2004 Apr 1;294(2):571-80
references: 15023543
references: Mol Biol Cell. 2010 Aug 1;21(15):2568-77
references: 20534813
references: Cancer Res. 2000 Jun 1;60(11):2949-54
references: 10850442
references: Bone. 2004 Sep;35(3):664-72
references: 15336602