LAMININ-5. A POTENTIAL TOOL IN DIAGNOSIS OF HEAD AND NECK SQUAMOUS CELL CARCINOMA
Abstract
The heterotrimeric extracellular matrix protein laminin-5 (ln-5) is a regular constituent of the basement membrane in oral and pharyngeal mucosa consisting of the α 3, β 3 and γ 2 chain. On the one hand, it is an integral part of the epithelial adhesion complex which connects the hemidesmosomes of the basal cells with the basement membrane. In this position, ln-5 strictly acts against migration and invasion and may fundamentally contribute to the distinction between intraepithelial neoplasia vs. invasive carcinoma. On the other hand, single chains of ln-5, in particular the γ 2 chain, are able to promote migration. The immunohistochemical ln-5 demonstration outside the basement membrane in the keratinocyte cytoplasm or in the stroma of the invasive front, as well as ln-5 synthesis, indicate epithelial cells potentially able to migrate and to invade. The extent of the ln-5 demonstration outside the basement membrane, as well the loss of ln-5 from the basement membrane, is therefore of prognostic value.
A diagnostic interpretation of ln-5 immunostainings has to consider the contrary functions of ln-5 or ln-5 fragments: within the basement membrane it acts as anchoring protein and outside the basement membrane it represents a migration/ invasion factor.
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References
Burgeson RE, Chiquet M, Deutzmann R et al. A new nomenclature for the laminins. Matrix Biol 1994; 14: 209–11.
Colognato H, Yurchenco PD. Form and function: the laminin family of heterodimers. Developmental Dynamics 2000; 218: 213–34.
Kosmehl H, Berndt A, Katenkamp D. Molecular variants of fibronectin and laminin: structure, physiological occurrence and histopathological aspects. Virchows Arch 1996; 429: 311–22.
Rousselle P, Lunstrum GP, Keene DR, Burgeson RE. Kalinin: an epithelium – specific basement membrane adhesion molecule that is a component of anchoring filaments. J Cell Biol 1991; 114: 567–76.
Carter WG, Ryan MC, Gahr PJ, Epiligran, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes. Cell 1991; 65: 599–610.
Meneguzzi G, Marinkovich MP, Aberdam D, Pisani A, Burgeson R, Ortone JP. Kalinin is abnormally expressed in epithelial basement membranes of Herliltz junctional, epidermiolysis bullosa patients. Exp Dermatol. 1992; 1: 221–9.
Miyazaki K, Kikkawa Y, Nakamura A, Yasumitsu H, Umeda M. A large celladhesive scatter factor secreted by human gastric carcinoma cells. Proc Natl Acad Sci USA 1993; 90: 11 767–71.
Lohi J, Leivo I, Owaribe K. Burgeson RE, Franssila K, Virtanen I. Neoexpression of the epithelial adhesion complex antigens in thyroid tumours is associated with proliferation and squamous differentiation markers. J Pathol 1998; 184: 191–6.
Gerecke DR, Gordon MK, Wagman DW, Champliaud MF, Burgeson RE Hemidesmosomes, anchoring filaments and anchoring fibrils: components of a unique attachment complex. In: Yurchenco PD, Bird DE, Mecham RP eds. Extracellular matrix assembly and structure. New York: Academic Press 1994: 417–39.
Baker SE, Hopkinson SB, Fitchmun M et al. Laminin-5 and hemidesmosomes: role of the (3 chain subunit in hemidesmosome stability and assembly. J Cell Sci 1996; 109: 2509–20.
Uitto J, Pulkkinen L, Christiano AM. Molecular basis of the dystrophic and junctional forms of epidermolysis bullosa: mutations in the type VII collagen and kalinin (laminin-5) genes. J Invest Dermatol 1994; 103: 39S–46S
Pulkkinen L, Cserhalmi-Friedmann PB, Tang M, Ryan MC, Uitto J, Christiano AM. Molecular analysis of the human laminin α3a chain gene (LAMA 3a): a strategy for mutation identification and DNA-based prenatal diagnosis in Herlitz junctional epidermolysis bullosa. Lab Invest 1998; 78: 1067–76.
Moll R, Moll I. Epidermal adhesion molecules and basement membrane components as target structures of autoimmunity. Virchows Arch 1998; 432: 487–504.
Haas M, Berndt A, Hyckel P, Stiller KJ, Kosmehl H. Laminin-5 bei Erkrankungen der Mundhöhle. Mund Kiefer Gesichts Chir 2000; 4: 25–9.
Tani T, Karttunen T, Kiviluoto T et al. α6β4 integrin and newly deposited laminin-1 and laminin-5 form the adhesion mechanism of gastric carcinoma. Continuous expression of laminins but not that of collagen VII is preserved in invasive parts of the carcinomas: implications for acquisition of the invading phenotype. Am J Pathol 1996; 149: 781–93.
Zhang H, Kramer RH. Laminin-5 deposition promotes keratinocyte motility. Exp Cell Res 1996; 227: 309–22.
Tani T, Lumme A, Linnala A et al. Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane. Am J Pathol 1997; 151: 1289–1302.
Goldfinger LE, Stacks MS, Jones JCR. Processing of laminin-5 and its functional consequences: role of plasmin and tissue-type plasminogen-activator. J Cell Biol 1998; 141: 255–65.
Hirosaki T, Mizushima H, Tsubota Y, Moriyama K, Miyazaki K. Structural requirement of carboxyl-terminal globular domains of laminin (3 chains for promotion of rapid cell adhesion and migration by laminin-5. Biol Chem 2000; 275: 22495–502.
Giannelli G, Falk-Marzillier J, Schiraldi O, Stetler-Stevenson WG, Quaranta V. Introduction of cell migration by matrix metalloprotease-2-cleavage of laminin-5. Science 1997; 277: 225–8.
Koshikawa N, Gianelli G, Cirulli V, Miyazaki K, Quaranta V. Role of cell surface metalloprotease MT1-MMP in epithelial cell migration over laminin5. J. Cell Biol 2000; 148: 615–24.
Sasaki T, Gohring W, Mann K et al. Short arm region of laminin-5 γ2chain: structure, mechanism of processing and binding to heparin and proteins. J Mol Biol 2001; 314: 751–63.
Haapasalmi K, Makela M, Osakala O et al. Expression of epithelial adhesion proteins and integrins in chronic inflammation. Am J Pathol 1995; 147: 193– 206.
Berndt A, Hyckel P, Könneker A, Katenkamp D, Kosmehl H. Oral squamous cell carcinoma invasion is associated with a laminin-5 matrix re-organisation but independent of basement membrane and hemidesmosome formation. Invasion Metastasis 1997;17: 251–8.
Matsui C, Nelson CF, Hernandez GT, Herron GS, Bauer EA, Hoeffler WK. γ2 chain of laminin-5 is recognized by monoclonal antibody GB3. J Invest Dermatol 1995; 105: 648–52.
Mizushima H, Koshikawa N, Moriyama K et al. Wide distribution of laminin5 (γ2 chain in basement membranes of various human tissues. Horm Res 1998; 50: 7–14.
Lohi J. Laminin-5 in the progression of carcinomas. Int J Cancer 2001; 94: 763–7.
Kosmehl H, Berndt A, Strassburger S et al. Distribution of laminin and fibronektin isoforms in oral mucosa and oral squamous cell carcinoma. Brit J Canc 1999; 81: 1071–9.
Pyke C, Roemer J, Kallunki P et al. The γ2 chain of kalinin/laminin-5 is preferentially expressed in invading malignant cells in human cancers. Am J Pathol 1994; 145: 782–91.
Kainulainen T, Autio-Harmainen H, Oikarinen A, Salo S, Tryggvason K, Salo T. Altered distribution and synthesis of Laminin-5 (kalinin) in oral lichen planus, epithelial dysplasias and squamous cell carcinomas. Br J Dermatol 1997; 136: 331–6.
Thorup AK, Dabelsteen E, Schou S, Gil SG, Carter WG, Reibel J. Differential expression of integrins and laminin-5 in normal oral epithelia. APMIS 1997; 105: 519–30.
Thorup AK, Reibel J, Schiodt M et al. Can alterations in integrin and laminin5 expression be used as markers of malignancy? APMIS 1998; 106: 1070–80.
Kainulainen T, Hakkinen L, Hamidi S et al. Laminin –5 expression is independent of the injury and the microenvironment during reepithelialization of wounds. J Histochem Cytochem 1998; 46: 353–60.
Skyldberg B, Salo S, Eriksson E et al. Laminin-5 is a marker of invasiveness in cervical lesions. J Natl Cancer Inst 1999; 91: 1882–7.
Nordemar S, Kronenwett U, Auer G et al. Laminin-5 as a predictor of invasiveness in cancer in situ lesions of the larynx. Anticancer Res 2001; 21: 509–12.
Hlubek F, Jung A, Kotzor N, Kirchner T, Brabletz T. Expression of the invasion factor laminin (2 in colorectal carcinomas is regulated by catenin. Cancer Res 2001; 61: 8089–93.
Berndt A, Borsi L, Hyckel P, Kosmehl H. Fibrillary co-deposition of laminin5 and large unspliced tenascin-C in the invasive front of oral squamous cell carcinoma in vivo and in vitro. J Cancer Res Clin Oncol 2001; 127: 286–92.
Ono Y, Nakanishi Y, Ino Y et al. Clinicopathologic significance of laminin5 (γ2 chain) in squamous cell carcinoma of the tongue. Cancer 1999; 85: 2315–21.
Patel V, Aldridge K, Ensley JF et al. Laminin γ2 overexpression in head and neck squamous cell carcinoma. Int J Cancer 2002; 99: 583–8.
Kosmehl H, Berndt A, Katenkamp D et al. Integrin receptors and their relationship to cellular proliferation and differentiation of oral squamous cell carcinoma. A quantitative immunohistochemical study. J Oral Pathol Med 1995; 24: 343–8.
Haas M, Berndt A, Stiller KJ, Hyckel P, Kosmehl H. A comparative analysis of laminin-5 in the basement membrane of normal, hyperplastic and malignant oral mucosa by confocal immunofluorescence imaging. J Histochem Cytochem 2001; 49 (10): 1261–88.
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