title: Podoplanin expression during dysplasia-carcinoma sequence in the oral cavity.
abstract: Human podoplanin, a type-1 transmembrane sialomucin-like glycoprotein, is involved in cell migration, tumor cell invasion, and metastasis. However, the role of the protein in squamous cell carcinoma (SCC) has been unclear and immunohistochemical reactivity for podoplanin differs from organ-to-organ. In the present study, immunohistochemical and molecular biological analyses were performed to examine the importance of podoplanin expression in oral precancerous and cancerous lesions and metastases. We immunohistochemically investigated the expression of podoplanin in 103 precancerous lesions, 69 primary oral squamous cell carcinomas (OSCCs), and 32 metastases, and that of E-cadherin and vimentin in primary OSCCs with metastasis. Furthermore, human OSCC-derived cell lines preincubated with fibrous growth factor-basic, epidermal growth factor (EGF), and tumor growth factor-β1 were subjected to real-time reverse transcription polymerase chain reaction. Immunoreactivity for podoplanin was detected in 89 (86.4%) of the precancerous lesions and the intensity was correlated with the degree of epithelial dysplasia (P = 0.016). Enhanced podoplanin expression was observed in 66 (95.7%) of the OSCCs and was significantly associated with a poor pathologic grade of differentiation (P = 0.020). Epithelial-mesenchymal transition was observed in 18 (58.1%) of the primary OSCCs with metastasis to regional lymph nodes. Messenger RNA for podoplanin was markedly increased after treatment with EGF in three OSCC cell lines. The present findings suggest that podoplanin is associated with tumor development via the oral dysplasia-carcinoma sequence and could be involved in a signaling pathway governing tumor growth and invasion in OSCC.
authors.affiliation: Division of Pathology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Keyakidai, Sakado, Saitama 350-0283, Japan. harumi-i@dent.meikai.ac.jp
authors.forename: Harumi
authors.initials: H
authors.lastname: Inoue
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yoshida
authors.forename: Fumio
authors.initials: F
authors.lastname: Ide
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohmori
authors.forename: Akihito
authors.initials: A
authors.lastname: Tomomura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sakashita
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kusama
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009055:Mouth / Q000378:metabolism / Q000473:pathology*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D000098853:Podoplanin
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; C117468:PDPN protein, human; D000098853:Podoplanin
references.citation: J Biol Chem. 2010 Mar 26;285(13):9649-9656
references.pmid: 20123990
references.citation: Mod Pathol. 2003 Oct;16(10):1028-34
references.pmid: 14559986
references.citation: Cancer Res. 2008 Sep 1;68(17):6877-83
references.pmid: 18757399
references.citation: Cancer Sci. 2009 Nov;100(11):2054-9
references.pmid: 19681903
references.citation: Br J Cancer. 2007 Jan 15;96(1):1-5
references.pmid: 17179989
references.citation: J Clin Invest. 1989 Jun;83(6):2025-33
references.pmid: 2498394
references.citation: J Oral Sci. 2009 Jun;51(2):283-7
references.pmid: 19550098
references.citation: Anat Sci Int. 2006 Dec;81(4):201-9
references.pmid: 17176958
references.citation: Cell Cycle. 2010 Jul 1;9(13):2499-500
references.pmid: 20647778
references.citation: Ann Surg Oncol. 2010 May;17(5):1311-23
references.pmid: 20066519
references.citation: J Oral Pathol Med. 2008 Mar;37(3):127-33
references.pmid: 18251935
references.citation: J Oral Pathol Med. 2010 Jan;39(1):110-4
references.pmid: 19925582
references.citation: Anticancer Res. 2008 Sep-Oct;28(5B):2997-3006
references.pmid: 19031946
references.citation: Pathobiology. 2011;78(3):171-80
references.pmid: 21613804
references.citation: EMBO J. 2003 Jul 15;22(14):3546-56
references.pmid: 12853470
references.citation: Cancer Sci. 2008 Jan;99(1):54-61
references.pmid: 17944973
references.citation: Mod Pathol. 2006 May;19(5):708-16
references.pmid: 16528371
references.citation: Cancer Cell. 2004 Apr;5(4):311-6
references.pmid: 15093538
references.citation: Int J Cancer. 2005 Mar 1;113(6):899-910
references.pmid: 15515019
references.citation: Histol Histopathol. 2009 Aug;24(8):1021-7
references.pmid: 19554509
references.citation: J Pathol. 1996 Apr;178(4):415-21
references.pmid: 8691320
references.citation: Am J Surg Pathol. 2008 Jan;32(1):123-7
references.pmid: 18162779
references.citation: J Biol Chem. 2003 Aug 22;278(34):31574-83
references.pmid: 12771142
references.citation: Cancer. 2006 Aug 1;107(3):563-9
references.pmid: 16804930
references.citation: Nat Genet. 1998 Aug;19(4):361-5
references.pmid: 9697697
references.citation: J Oral Pathol Med. 2010 Jan;39(1):103-9
references.pmid: 19691459
references.citation: Acta Neuropathol. 2006 May;111(5):483-8
references.pmid: 16596424
references.citation: Mol Cancer. 2010 Mar 02;9:48
references.pmid: 20196862
references.citation: Int J Gynecol Pathol. 2010 Sep;29(5):405-10
references.pmid: 20736762
references.citation: N Engl J Med. 2001 Apr 26;344(17):1323-6
references.pmid: 11320393
references.citation: Cancer Res. 1983 Apr;43(4):1696-702
references.pmid: 6403227
references.citation: Am J Pathol. 2005 Mar;166(3):913-21
references.pmid: 15743802
references.citation: J Clin Oncol. 2008 Jan 20;26(3):354-60
references.pmid: 18202409
references.citation: Am J Respir Cell Mol Biol. 1996 Jun;14(6):577-85
references.pmid: 8652186
references.citation: Cancer Res. 1992 Sep 1;52(17):4773-8
references.pmid: 1380891
references.citation: Virchows Arch. 2006 Aug;449(2):200-6
references.pmid: 16736189
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4336-44
references.pmid: 18594017
references.citation: Bone. 1996 Feb;18(2):125-32
references.pmid: 8833206
references.citation: Am J Pathol. 1999 Feb;154(2):385-94
references.pmid: 10027397
references.citation: Virchows Arch. 2006 Apr;448(4):493-9
references.pmid: 16411134
references.citation: Cancer Cell. 2006 Apr;9(4):261-72
references.pmid: 16616332
references.citation: Virchows Arch. 2010 May;456(5):473-82
references.pmid: 20393745
references.citation: Am J Pathol. 1997 Oct;151(4):1141-52
references.pmid: 9327748
references.citation: J Biol Chem. 2003 Nov 21;278(47):46533-40
references.pmid: 12972425
references.citation: Histopathology. 2000 Jul;37(1):93-4
references.pmid: 10931742