Abstract
The distribution of αvβ6integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins β1, β3, β4, β5, fibronectin and tenascin were also studied. The integrin αvβ6was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. αvβ6integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of β1 integrins was localized in the basal layer, and that of the β4at the cell surface facing the basement membrane of all specimens. The integrins β3and β5were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both αvβ6-positive and αvβ6-negative tissues. A group of 28 leukoplakia patients were followed 1–4 years after first diagnosis. In this group, initially αvβ6integrin-positive leukoplakia specimens had high tendency for disease progression while αvβ6-negative specimens did not progress. These results suggest that the expression of αvβ6integrin could be associated in the malignant transformation of oral leukoplakias. © 2000 Cancer Research Campaign
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References
Adams JC and Watt FM (1991) Expression of β1, β3, β4, β5integrins by human epidermal keratinocytes and non-differentiating keratinocytes. J Cell Biol 115: 829–841
Agrez MV, Bates RC, Mitchell D, Wilson N, Ferguson N, Anseline P and Sheppard D (1996) Multiplicity of fibronectin-binding αvintegrin receptors in colorectal cancer. Br J Cancer 73: 887–892
Beck JD (1995) Issues in assessment of diagnostic tests and risk for periodontal diseases. Periodontol 2000 7: 100–108
Breuss JM, Gillett N, Lu L, Sheppard D and Pytela R (1993) Restricted distribution of integrin β6mRNA in primate epithelial tissues. J Histochem Cytochem 41: 1521–1527
Breuss JM, Gallo J, DeLisser HM, Klimanskaya IV, Folkesson HG, Pittet JF, Nishimura SL, Aldape K, Landers DV, Carpenter W, Gillett N, Sheppard D, Matthay MA, Albelda SM, Kramer RH and Pytela R (1995) Expression of the β6integrin subunit in development, neoplasia and tissue repair suggests a role in epithelial remodeling. J Cell Sci 108: 2241–2251
Carter WG, Wayner EA, Bouchard TS and Kaur P (1990) The role of integrins α2β1and α3β1in cell–cell and cell–substrate adhesion of human epidermal cells. J Cell Biol 110: 1387–1404
Clark RAF, Ashcroft GS, Spencer MJ, Larjava H and Ferguson MWJ (1996) Reepithelialization of normal human excisional wounds is associated with a switch from αvβ5to αvβ6integrins. Br J Dermatol 135: 46–51
Cui W, Fowlis DJ, Bryson S, Duffie E, Ireland H, Balmain A and Akhurst RJ (1996) TGFβ1inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 86: 531–542
Damjanovich L, Albelda SM, Mette SA and Buck CA (1992) Distribution of integrin cell adhesion receptors in normal and malignant lung tissue. Am J Respir Cell Mol Biol 6: 197–206
Downer CS, Watt FM and Speight PM (1993) Loss of α6and β4integrin subunits coincides with loss of basement membrane components in oral squamous cell carcinoma. J Pathol 171: 183–190
Feliciani C, Gupta AK and Sauder DN (1996) Keratinocytes and cytokine/growth factors. Crit Rev Biol Med 7: 300–318
Gallo O, Santucci M and Franchi A (1997) Cumulative prognostic value of p16/CDKN2 and p53 oncoprotein expression in premalignant laryngeal lesions. J Natl Cancer 15: 1161–1163
Gui GPH, Wells CA, Browne PD, Yeomans P, Jordan S, Puddefoot JR, Vinson GP and Carpenter R (1995) Integrin expression in primary breast cancer and its relation to axillary nodal status. Surgery 117: 102–108
Gupta PC, Mehta FS, Daftary DK, Pindborg JJ, Bhonsle RB, Jalnawalla PN, Sinor PN, Pitkar VK, Murti PR, Irani RR, Shah HT, Kadam PM, Iyer KS, Iyer HM, Hegde AK, Chandrashekar GK, Shiroff BC, Sahiar BE and Mehta MN (1980) Incidence rates of oral cancer and natural history of oral precancerous lesions in a 10-year follow-up study of Indian villagers. Community Dent Oral Epidemiol 8: 287–233
Haapalainen T, Oksala O, Kallioinen M, Oikarinen A, Larjava H and Salo T (1995) Destruction of epithelial anchoring system in lichen planus. J Invest Dermatol 105: 100–103
Haapasalmi K, Mäkelä M, Oksala O, Heino J, Yamada KM, Uitto VJ and Larjava H (1995) Expression of epithelial adhesion proteins and integrins in chronic inflammation. Am J Pathol 147: 193–206
Haapasalmi K, Zhang K, Tonnesen M, Olerud J, Sheppard D, Salo T, Kramer R, Clark RAF, Uitto VJ and Larjava H (1996) Keratinocytes in human wounds express αvβ6integrin. J Invest Dermatol 106: 42–48
Houghton AN, Eisenger M, Albino AP, Cairncross JG and Old LJ (1982) Surface antigens of melanocytes and melanomas. Markers of melanocyte differentiation and melanoma subsets. J Exp Med 156: 1755–1766
Huang XZ, Wu JF, Cass D, Erle DJ, Corry D, Young SG, Farese, Jr RV and Sheppard D (1996) Inactivation of the integrin β6subunit gene reveals a role of epithelial integrins in regulating inflammation in the lungs and skin. J Cell Biol 133: 921–928
Jensen HM, Chen I, DeVault MR and Lewis AE (1982) Angiogenesis induced by ‘normal’ human breast tissue: a probable marker for precancer. Science 218: 293–295
Jones J, Watt FM and Speight PM (1997) Changes in the expression of αvintegrins in oral squamous cell carcinomas. J Oral Path Med 26: 63–68
Kobayashi T and Kawakubo T (1994) Prospective investigation of tumor markers and risk assessment in early cancer screening. Cancer 73: 1946–1953
Koretz K, Schlag P, Boumsell L and Möller P (1991) Expression of VLA-α2, VLA-α6, and VLA-β1chains in normal mucosa and adenomas of the colon, and in colon carcinomas and their liver metastases. Am J Pathol 138: 741–750
Koivisto L, Grenman R, Heino J and Larjava H (Integrins α5β1, αvβ1and αvβ6in squamous carcinoma cell spreading and migration on fibronectin. Exp Cell Res (in press)
Koukoulis GK, Virtanen I, Korhonen M, Laitinen L, Quaranta V and Gould VE (1991) Immunohistochemical localization of integrins in the normal, hyperplastic and neoplastic breast. Am J Pathol 139: 787–799
Larjava H, Haapasalmi K, Salo T, Wiebe C and Uitto V-J (1996) Keratinocyte integrins in wound healing and chronic inflammation of the human periodontium. Oral Diseases 2: 77–86
Larjava H, Salo T, Haapasalmi K, Kramer RH and Heino J (1993) Expression of integrins and basement membrane components by wound keratinocytes. J Clin Invest 92: 1425–1435
Liebert M, Washington R, Stein J, Wedemeyer G and Grossman HB (1994) Expression of the VLA β1integrin family in bladder cancer. Am J Pathol 144: 1016–1022
Morson BC (1985) Precancer and cancer in inflammatory bowel disease. Pathology 17: 173–180
Munger JS, Huang X, Kawakatsu H, Griffiths MJ, Dalton SL, Wu J, Pittet JF, Kaminski N, Garat C, Matthay MA, Rifkin DB and Sheppard D (1999) The integrin αvβ6binds and activates latent TGF-β1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell 96: 319–328
Nigam AK, Savage FJ, Boulos PB, Stamp GWH, Liu D and Pignatelli M (1993) Loss of cell–cell and cell–matrix adhesion molecules in colorectal cancer. Br J Cancer 68: 507–514
Palecek SP, Loftus JG, Ginsberg MH, Lauffenburger DA and Horwitz AF (1997) Integrin–ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385: 537–540
Peltonen J, Larjava H, Jaakkola S, Gralnick H, Akiyama SK, Yamada SS, Yamada KM and Uitto J (1989) Localization of integrin receptors for fibronectin, collagen, and laminin in human skin. J Clin Invest 84: 1916–1923
Pignatelli M, Smith MEF and Bodmer WF (1990) Low expression of collagen receptors in moderate and poorly differentiated colorectal adenocarcinomas. Br J Cancer 61: 636–638
Pignatelli M, Hanby AM and Stamp GWH (1991) Low expression of β1, α2and α3subunits of VLA integrins in malignant mammary tumors. J Pathol 165: 25–32
Prieto AL, Edelman GM and Crossin KL (1993) Multiple integrins mediate cell attachment to cytotactin/tenascin. Proc Natl Acad Sci USA 90: 10154–10158
Ruoslahti E (1991) Integrins. J Clin Invest 87: 1–5
Scully C, Beyli M, Ferreiro MC, Ficarra G, Gill Y, Griffiths M, Homstrup P, Mutlu S, Porter S and Wray D (1998) Update on oral lichen planus: etiopathogenesis and management. Crit Rev Oral Biol Med 9: 86–122
Sheppard D (1996) Epithelial integrins. Bio Essays 18: 655–660
Sheppard D, Rozzo C, Starr L, Quaranta V, Erle DJ and Pytela R (1990) Complete amino acid sequence of a novel integrin β subunit (β6) identified in epithelial cells using the polymerase chain reaction. J Biol Chem 265: 11502–11507
Silverman S Jr, Gorsky M and Lazada F (1984) Oral leukoplakia and malignant transformation. A follow-up study of 257 patients. Cancer 53: 563–568
Sonnenberg A, Calafat J, Janssen H, Daams H, van der Raaij-Helmer LMH, Falcioni R, Kennel SJ, Aplin JD, Baker J, Loizidou M and Garrod D (1991) Integrin α6β4complex is located in hemidesmosomes, suggesting a major role in epidermal cell–basement membrane adhesion. J Cell Biol 113: 907–917
Staquet MJ, Levarlet B, Dezutter-Dambuyant C, Schmitt D and Thivolet J (1990) Identification of specific human epithelial cell integrin receptors as VLA proteins. Exp Cell Res 187: 277–283
Stepp MA, Spurr-Michaud S, Tisdale A, Elwell J and Gipson IK (1990) α6β4integrin heterodimer is a component of hemidesmosomes. Proc Natl Acad Sci USA 87: 8970–8974
Watt FM and Jones PH (1993) Expression and function of the keratinocyte integrins. Development Suppl 185–192
Weinacker A, Ferrando R, Elliott M, Hogg J, Balmes J and Sheppard D (1995) Distribution of integrins αvβ6and α9β1and their known ligands, fibronectin and tenascin, in human airways. Am J Respir Cell Mol Biol 12: 547–556
WHO (1997) Histological Typing of Cancer and Precancer of Oral Mucosa. Springer: New York
Yamamoto T and Osaki T (1995) Characteristic cytokines generated by keratinocytes and mononuclear infiltrates in oral lichen planus. J Invest Dermatol 5: 784–788
Yamamoto T, Osaki T, Yoneda K and Ueta E (1993) An immunological investigation on adult patients with primary herpes simplex virus-1 infection. J Oral Pathol Med 22: 263–267
Yang GY and Shamsuddin AM (1996) Gal-GalNAc: a bio-marker of colon carcinogenesis. Histol Histopathol 11: 801–806
Zambruno G, Marchisio PC, Marconi A, Vaschieri C, Melchiori A, Giannetti A and De Luca M (1995) Transforming growth factor-β1modulates β1and β5integrin receptors and induces the de novo expression of the αvβ6heterodimer in normal keratinocytes: implications for wound healing. J Cell Biol 129: 853–865
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Hamidi, S., Salo, T., Kainulainen, T. et al. Expression of αvβ6integrin in oral leukoplakia. Br J Cancer 82, 1433–1440 (2000). https://doi.org/10.1054/bjoc.1999.1130
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DOI: https://doi.org/10.1054/bjoc.1999.1130
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