title: A novel orthotopic mouse model of head and neck cancer and lymph node metastasis.
abstract: Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be controlled by cancer cell genetics. To examine the role of these genes in LN metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed comparative microarray analysis of gene expression between populations of HNSCC cell lines derived before and after serial transplantation and in vivo metastasis in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC-HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial-to- mesenchymal transition and the formation of cancer stem cells, including CAV-1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT-4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in HNSCC cells selected for an enhanced metastatic phenotype and suggest that these genes may have an important role in the metastatic potential of HNSCC cells. Inhibition of these genes may therefore have prognostic and therapeutic utility in HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Masood
authors.forename: C
authors.initials: C
authors.lastname: Hochstim
authors.forename: B
authors.initials: B
authors.lastname: Cervenka
authors.forename: S
authors.initials: S
authors.lastname: Zu
authors.forename: S K
authors.initials: SK
authors.lastname: Baniwal
authors.forename: V
authors.initials: V
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Kobielak
authors.forename: U K
authors.initials: UK
authors.lastname: Sinha
references.citation: Cancer Res. 2009 Apr 1;69(7):3105-13
references.pmid: 19318560
references.citation: J Chin Med Assoc. 2012 Jun;75(6):269-74
references.pmid: 22721621
references.citation: Nat Rev Cancer. 2003 Oct;3(10):733-44
references.pmid: 14570033
references.citation: Stem Cells. 2012 Oct;30(10):2100-13
references.pmid: 22887839
references.citation: Biochem Biophys Res Commun. 2011 Nov 18;415(2):245-51
references.pmid: 22037460
references.citation: Clin Cancer Res. 2011 Apr 15;17(8):2350-60
references.pmid: 21220476
references.citation: J Cell Biochem. 2011 Sep;112(9):2508-17
references.pmid: 21557297
references.citation: Head Neck Oncol. 2009 Aug 13;1:32
references.pmid: 19678942
references.citation: J Oral Pathol Med. 2003 Sep;32(8):461-7
references.pmid: 12901727
references.citation: Gastroenterology. 2011 Jul;141(1):279-91, 291.e1-5
references.pmid: 21640118
references.citation: Exp Biol Med (Maywood). 2006 Jan;231(1):20-7
references.pmid: 16380641
references.citation: Cancer Cell. 2009 Mar 3;15(3):207-19
references.pmid: 19249679
references.citation: Cancer. 1994 Jul 15;74(2):565-72
references.pmid: 8033034
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 1;103(31):11707-12
references.pmid: 16857736
references.citation: Carcinogenesis. 2006 May;27(5):1113-20
references.pmid: 16474169
references.citation: Science. 2011 Aug 26;333(6046):1157-60
references.pmid: 21798893
references.citation: BMC Med. 2012 Aug 31;10:98
references.pmid: 22938142
references.citation: Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1197-203
references.pmid: 12775576
references.citation: Clin Exp Metastasis. 2006;23(3-4):209-22
references.pmid: 17028921
references.citation: Cancer. 2008 Jun 15;112(12):2710-9
references.pmid: 18481809
references.citation: J Clin Oncol. 2006 Dec 20;24(36):5630-6
references.pmid: 17179101
references.citation: Int J Oncol. 2009 May;34(5):1433-48
references.pmid: 19360357
references.citation: Cell Cycle. 2011 May 1;10(9):1378-84
references.pmid: 21552008
references.citation: Science. 2011 Aug 26;333(6046):1154-7
references.pmid: 21798897
references.citation: Anticancer Res. 2012 Apr;32(4):1163-6
references.pmid: 22493345
references.citation: Cancer Cell. 2003 Dec;4(6):499-515
references.pmid: 14706341
references.citation: Eur J Histochem. 2010 Apr 14;54(2):e20
references.pmid: 20558341
references.citation: Head Neck Oncol. 2010 Feb 22;2:5
references.pmid: 20175927
references.citation: CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108
references.pmid: 15761078
references.citation: Oral Oncol. 2012 Jan;48(1):1-9
references.pmid: 22070916
references.citation: Asian Pac J Cancer Prev. 2011;12(2):397-401
references.pmid: 21545202
references.citation: Cancer. 2002 Oct 15;95(8):1663-72
references.pmid: 12365014
references.citation: Biomaterials. 2012 May;33(14):3693-709
references.pmid: 22361100
references.citation: J Clin Invest. 2003 Dec;112(12):1776-84
references.pmid: 14679171
references.citation: J Gastroenterol Hepatol. 2012 Mar;27 Suppl 2:19-22
references.pmid: 22320911
references.citation: Cancer Res. 2004 Nov 1;64(21):7977-84
references.pmid: 15520205