title: Animal models in osteosarcoma.
abstract: Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in children and adults. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for non-metastatic disease approaching 70%. However, most OS tumors are high grade and tend to rapidly develop pulmonary metastases. Despite clinical advances, patients with metastatic disease or relapse have a poor prognosis. Toward a better understanding of the molecular pathogenesis of human OS, several genetically modified OS mouse models have been developed and will be reviewed here. However, better animal models that more accurately recapitulate the natural progression of the disease are needed for the development of improved prognostic and diagnostic markers as well as targeted therapies for both primary and metastatic OS.
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Florida , Gainesville, FL , USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Guijarro
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Florida , Gainesville, FL , USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Ghivizzani
authors.affiliation: Department of Orthopaedics and Rehabilitation, University of Florida , Gainesville, FL , USA.
authors.forename: C Parker
authors.initials: CP
authors.lastname: Gibbs
keywords: RB; animal models; conditional mouse models; germ-line mouse models; osteosarcoma; p53
references.citation: Nature. 2007 Aug 23;448(7156):943-6
references.pmid: 17713536
references.citation: Nature. 1986 Oct 16-22;323(6089):643-6
references.pmid: 2877398
references.citation: Development. 2006 Aug;133(16):3231-44
references.pmid: 16854976
references.citation: BMC Med Genomics. 2011 Sep 20;4:66
references.pmid: 21933437
references.citation: Cancer Res. 2001 May 1;61(9):3750-9
references.pmid: 11325848
references.citation: Cancer Invest. 2009 May;27(4):435-42
references.pmid: 19212826
references.citation: Cancer Genet Cytogenet. 2003 Aug;145(1):1-30
references.pmid: 12885459
references.citation: Eur J Cancer. 1979 Sep;15(9):1151-8
references.pmid: 294355
references.citation: Carcinogenesis. 2009 Oct;30(10):1789-95
references.pmid: 19635748
references.citation: Nature. 1992 Mar 19;356(6366):215-21
references.pmid: 1552940
references.citation: Oncogene. 1989 Jul;4(7):861-5
references.pmid: 2547184
references.citation: Nat Genet. 1994 Aug;7(4):480-4
references.pmid: 7951317
references.citation: Cancer Genet Cytogenet. 1994 Oct;77(1):81-8
references.pmid: 7923089
references.citation: Drugs. 1994 Jan;47(1):82-92
references.pmid: 7510623
references.citation: J Clin Oncol. 2012 Jan 1;30(1):78-84
references.pmid: 22067397
references.citation: Cancer Res. 1992 Nov 15;52(22):6194-9
references.pmid: 1423262
references.citation: Cancer Res. 1993 Oct 15;53(20):4890-5
references.pmid: 8402677
references.citation: Cancer Treat Res. 2009;152:467-78
references.pmid: 20213409
references.citation: Am J Pathol. 1980 Jan;98(1):285-8
references.pmid: 6927951
references.citation: Nature. 1992 Sep 24;359(6393):288-94
references.pmid: 1406932
references.citation: Acta Unio Int Contra Cancrum. 1959;15:559-60
references.pmid: 13799020
references.citation: Genes Dev. 2008 Jun 15;22(12):1662-76
references.pmid: 18559481
references.citation: Cancer Res. 1990 Dec 15;50(24):7950-4
references.pmid: 2253237
references.citation: Anticancer Res. 2002 Sep-Oct;22(5):2765-70
references.pmid: 12529994
references.citation: Cancer Lett. 1997 Jan 1;111(1-2):173-8
references.pmid: 9022143
references.citation: J Clin Oncol. 2012 Jan 20;30(3):256-62
references.pmid: 22184397
references.citation: Cancer. 2009 Apr 1;115(7):1531-43
references.pmid: 19197972
references.citation: Tijdschr Diergeneeskd. 1994 Dec 15;119(24):756-9
references.pmid: 7801309
references.citation: Nature. 1976 Apr 1;260(5550):436-8
references.pmid: 1062678
references.citation: J Cancer Res Clin Oncol. 1996;122(9):559-65
references.pmid: 8781571
references.citation: Cancer Res. 2006 Apr 1;66(7):3355-8, discussion 3358-9
references.pmid: 16585152
references.citation: Nat Rev Drug Discov. 2006 Sep;5(9):741-54
references.pmid: 16915232
references.citation: Front Oncol. 2013 May 31;3:132
references.pmid: 23755370
references.citation: Mol Cell. 2001 Aug;8(2):303-16
references.pmid: 11545733
references.citation: Nat Genet. 2013 Jul;45(7):799-803
references.pmid: 23727862
references.citation: Lancet Oncol. 2010 Jul;11(7):670-8
references.pmid: 20347613
references.citation: Genesis. 2002 Jun;33(2):77-80
references.pmid: 12112875
references.citation: Mol Cell Biol. 1989 Sep;9(9):3982-91
references.pmid: 2476668
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11851-6
references.pmid: 18697945
references.citation: Cancer Res. 2010 Jan 1;70(1):160-71
references.pmid: 20048075
references.citation: Eur J Cancer. 1979 May;15(5):685-91
references.pmid: 292595
references.citation: Vet Pathol. 2002 Mar;39(2):240-6
references.pmid: 12009062
references.citation: Nat Rev Cancer. 2007 Sep;7(9):645-58
references.pmid: 17687385
references.citation: Mol Cell Endocrinol. 2002 Nov 29;197(1-2):179-85
references.pmid: 12431811
references.citation: Cancer. 2012 Jan 15;118(2):558-70
references.pmid: 21713766
references.citation: CA Cancer J Clin. 1966 Jan-Feb;16(1):26-8
references.pmid: 4955730
references.citation: Cancer Treat Rev. 2014 May;40(4):523-32
references.pmid: 24345772
references.citation: Cancer Res. 2001 Aug 15;61(16):6234-8
references.pmid: 11507077
references.citation: BMC Genomics. 2009 Dec 23;10:625
references.pmid: 20028558
references.citation: Anim Genet. 2006 Jun;37(3):248-52
references.pmid: 16734685
references.citation: J Clin Invest. 2010 Sep;120(9):3310-25
references.pmid: 20697156
references.citation: Ann Surg Oncol. 2005 Dec;12(12):1073-83
references.pmid: 16252138
references.citation: Vet Pathol. 2002 May;39(3):372-8
references.pmid: 12014501
references.citation: Int J Cancer. 2001 Jan 20;95(1):34-8
references.pmid: 11241308
references.citation: Mol Cancer. 2009 Sep 07;8:72
references.pmid: 19735553
references.citation: Cell. 2004 Dec 17;119(6):847-60
references.pmid: 15607980
references.citation: Clin Exp Metastasis. 2000;18(3):261-71
references.pmid: 11315100
references.citation: Bone. 2010 Nov;47(5):859-65
references.pmid: 20696288
references.citation: Vet Surg. 2008 Jul;37(5):454-60
references.pmid: 18986312
references.citation: Proc Natl Acad Sci U S A. 1985 Sep;82(18):6216-20
references.pmid: 2994066
references.citation: Clin Sarcoma Res. 2012 Oct 04;2(1):19
references.pmid: 23036272
references.citation: Nature. 2010 Aug 26;466(7310):1110-4
references.pmid: 20686481
references.citation: Cell. 2004 Dec 17;119(6):861-72
references.pmid: 15607981
references.citation: Cancer Res. 1994 Jun 1;54(11):3042-8
references.pmid: 8187094
references.citation: Crit Rev Oncol Hematol. 2006 Oct;60(1):1-8
references.pmid: 16837208
references.citation: Anticancer Res. 2007 Jan-Feb;27(1A):155-64
references.pmid: 17352227
references.citation: Vet Pathol. 2000 Jan;37(1):54-61
references.pmid: 10643981
references.citation: Pediatr Blood Cancer. 2007 Dec;49(7):928-40
references.pmid: 17066459
references.citation: Carcinogenesis. 1998 Jan;19(1):213-7
references.pmid: 9472714
references.citation: Cancer Genet Cytogenet. 1996 Feb;86(2):136-42
references.pmid: 8603340
references.citation: Ann Oncol. 2012 Feb;23(2):508-16
references.pmid: 21527590
references.citation: J Orthop Res. 2001 May;19(3):339-45
references.pmid: 11398843
references.citation: Transl Oncol. 2010 Dec 01;3(6):344-53
references.pmid: 21151473
references.citation: Int J Cancer. 1999 Jan 18;80(2):199-204
references.pmid: 9935200
references.citation: Sarcoma. 2012;2012:417271
references.pmid: 22566751
references.citation: J Biol Chem. 1998 Nov 13;273(46):30509-16
references.pmid: 9804819
references.citation: Int J Cancer. 2009 Jul 1;125(1):229-34
references.pmid: 19330840
references.citation: Clin Exp Metastasis. 1997 Mar;15(2):164-72
references.pmid: 9062393
references.citation: Pediatr Blood Cancer. 2012 Mar;58(3):327-33
references.pmid: 21990244
references.citation: J Cell Biol. 2006 Mar 13;172(6):909-21
references.pmid: 16533949
references.citation: Curr Biol. 1994 Jan 1;4(1):1-7
references.pmid: 7922305
references.citation: Nature. 2001 Sep 6;413(6851):86-91
references.pmid: 11544531
references.citation: Bone. 2013 Jul;55(1):166-78
references.pmid: 23486187
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11547-52
references.pmid: 12972634
references.citation: J Cancer Res Clin Oncol. 2007 Mar;133(3):193-8
references.pmid: 17031670