© 1996 by Oxford University Press
Journal of the National Cancer Institute, Vol. 88, No. 7, 442-449,
April 3, 1996
© 1996 Oxford University Press
Changes in Integrin and E-Cadherin Expression in Neoplastic Versus Normal Thyroid Tissue
Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy
Department of Clinical and Biological Sciences, University of Torino Novara Branch
Department of Biomedical Sciences and Human Oncology, University of Torino, and Department of Medical Sciences, University of Torino Novara Branch
Department of Biological and Technological Research, San Raffaele Scientific Institute.
Correspondence to: Pier Carlo Marchisio, M.D., Ph.D., Department of Biological and Technological Research, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
BACKGROUND: The functional organization of polarized epithelia depends mostly on adhesion molecules belonging to the integrin and cadherin families. These molecules either recognize basement membrane components, such as laminins, or form intercellular junctions via homotypic interactions. Such tissue organization is often disrupted upon neoplastic transformation, and the resulting loss of functional polarization and cell cohesion might be a prerequisite for the invasive and metastatic behavior of carcinomas.
PURPOSE: We studied modifications of thyroid adhesive mechanisms at various stages of neoplastic progression in terms of adhesion molecule expression, topography, and functional regulation by tyrosine kinases. Starting from this working hypothesis, we sought to identify one or more biological markers that would be suggestive of malignant transformation and poorer prognosis and that could be developed as a reliable indicator(s) in early diagnostic steps.
METHODS: The study was carried out on both surgical samples and the corresponding fine-needle aspiration biopsy smears (numbers of specimens collected: 19 adenomas, seven follicular carcinomas, 13 papillary carcinomas, and 39 normal tissues). Immunohistochemistry of tissue sections and smears and immunoprecipitation and western blot analysis of protein extracts were done with a battery of monoclonal and polyclonal antibodies. Northern blotting was performed on RNA extracts from frozen tissue samples and use of an intergrin subunit 
4 complementary DNA probe.
RESULTS: Our findings can be summarized as follows: 1) In normal thyroid cells, the cooperative role of integrin 
64 and laminin 5/kalinin in hemidesmosome-mediated adhesion is missing, and recognition of the basal lamina occurs via integrin 31 and laminin 1 and/or 2 (this pattern being maintained in adenomas but altered in carcinomas regardless of their histotype or differentiation grade); 2) only in carcinomas with clinical and/or histologic aggressiveness do neoexpression of integrin subunit 4 and loss of laminin 2/merosin occur, indicating denovo assembly of integrin 64; 3) pericellular redistribution and cytoskeletal disconnection of the E-cadherin-catenin complex occur; and 4) basal E-cadherin tyrosine phosphorylation decreases in carcinomas as compared with that in normal and adenomatous tissues.
CONCLUSIONS: The malignant progression of thyroid tumors involves marked rearrangements of cell-basement membrane and cell—cell adhesion molecules and changes in their cytoskeleton linkage. These rearrangements are also easily and reproducibly detected on fine-needle aspiration biopsy smears.
IMPLICATIONS: Immunodetection of adhesion molecules in sections and/or fine-needle smears may complement the toolbox of thyroid surgical pathologists; it may expand the possibilities of achieving a correct early diagnosis of thyroid tumors and of gaining some prognostic information on thyroid tumors. [J Natl Cancer Inst 1996;88:442–9]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Bon, S. E. Di Carlo, V. Folgiero, P. Avetrani, C. Lazzari, G. D'Orazi, M. F. Brizzi, A. Sacchi, S. Soddu, G. Blandino, et al. Negative Regulation of {beta}4 Integrin Transcription by Homeodomain-Interacting Protein Kinase 2 and p53 Impairs Tumor Progression Cancer Res., July 15, 2009; 69(14): 5978 - 5986. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Hardy, C. Vicente-Duenas, I. Gonzalez-Herrero, C. Anderson, T. Flores, S. Hughes, C. Tselepis, J. A. Ross, and I. Sanchez-Garcia Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis Am. J. Pathol., September 1, 2007; 171(3): 1037 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bon, V. Folgiero, G. Bossi, L. Felicioni, A. Marchetti, A. Sacchi, and R. Falcioni Loss of {beta}4 Integrin Subunit Reduces the Tumorigenicity of MCF7 Mammary Cells and Causes Apoptosis upon Hormone Deprivation. Clin. Cancer Res., June 1, 2006; 12(11): 3280 - 3287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Oku, E. Sasabe, E. Ueta, T. Yamamoto, and T. Osaki Tight Junction Protein Claudin-1 Enhances the Invasive Activity of Oral Squamous Cell Carcinoma Cells by Promoting Cleavage of Laminin-5 {gamma}2 Chain via Matrix Metalloproteinase (MMP)-2 and Membrane-Type MMP-1. Cancer Res., May 15, 2006; 66(10): 5251 - 5257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Pegtel, A. Subramanian, T.-S. Sheen, C.-H. Tsai, T. R. Golub, and D. A. Thorley-Lawson Epstein-Barr-Virus-Encoded LMP2A Induces Primary Epithelial Cell Migration and Invasion: Possible Role in Nasopharyngeal Carcinoma Metastasis J. Virol., December 15, 2005; 79(24): 15430 - 15442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E Saggiorato, R De Pompa, M Volante, S Cappia, F Arecco, A P Dei Tos, F Orlandi, and M Papotti Characterization of thyroid 'follicular neoplasms' in fine-needle aspiration cytological specimens using a panel of immunohistochemical markers: a proposal for clinical application Endocr. Relat. Cancer, June 1, 2005; 12(2): 305 - 317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Hintermann, N. Yang, D. O'Sullivan, J. M. G. Higgins, and V. Quaranta Integrin {alpha}6{beta}4-erbB2 Complex Inhibits Haptotaxis by Up-regulating E-cadherin Cell-Cell Junctions in Keratinocytes J. Biol. Chem., March 4, 2005; 280(9): 8004 - 8015. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-C. Gerard, C. Daumerie, C. Mestdagh, S. Gohy, C. de Burbure, S. Costagliola, F. Miot, M.-C. Nollevaux, J.-F. Denef, J. Rahier, et al. Correlation between the Loss of Thyroglobulin Iodination and the Expression of Thyroid-Specific Proteins Involved in Iodine Metabolism in Thyroid Carcinomas J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4977 - 4983. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ishigaki, H. Namba, M. Nakashima, T. Nakayama, N. Mitsutake, T. Hayashi, S. Maeda, M. Ichinose, T. Kanematsu, and S. Yamashita Aberrant Localization of {beta}-Catenin Correlates with Overexpression of Its Target Gene in Human Papillary Thyroid Cancer J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3433 - 3440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morena, S. Riccioni, A. Marchetti, A. T. Polcini, A. M. Mercurio, G. Blandino, A. Sacchi, and R. Falcioni Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells Blood, June 17, 2002; 100(1): 96 - 106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Saggiorato, S. Cappia, P. De Giuli, A. Mussa, G. Pancani, P. Caraci, A. Angeli, and F. Orlandi Galectin-3 as a Presurgical Immunocytodiagnostic Marker of Minimally Invasive Follicular Thyroid Carcinoma J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5152 - 5158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mariotti, P. A. Kedeshian, M. Dans, A. M. Curatola, L. Gagnoux-Palacios, and F. G. Giancotti EGF-R signaling through Fyn kinase disrupts the function of integrin {alpha}6{beta}4 at hemidesmosomes: role in epithelial cell migration and carcinoma invasion J. Cell Biol., October 29, 2001; 155(3): 447 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Shaw Identification of Insulin Receptor Substrate 1 (IRS-1) and IRS-2 as Signaling Intermediates in the {alpha}6{beta}4 Integrin-Dependent Activation of Phosphoinositide 3-OH Kinase and Promotion of Invasion Mol. Cell. Biol., August 1, 2001; 21(15): 5082 - 5093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S M Ismail, S Vandeginste, and R W Shaw An unusually aggressive case of endometriosis showing p53 expression J. Clin. Pathol., May 1, 2001; 54(5): 396 - 398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Böhm, L. Niskanen, K. Kiraly, J. Kellokoski, M. Eskelinen, S. Hollmen, E. Alhava, and V.-M. Kosma Expression and Prognostic Value of {{alpha}}-, {beta}-, and {{gamma}}-Catenins in Differentiated Thyroid Carcinoma J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4806 - 4811. [Abstract] [Full Text]
|
|
|
|
|
|
D. Gambaletta, A. Marchetti, L. Benedetti, A. M. Mercurio, A. Sacchi, and R. Falcioni Cooperative Signaling between alpha 6beta 4 Integrin and ErbB-2 Receptor Is Required to Promote Phosphatidylinositol 3-Kinase-dependent Invasion J. Biol. Chem., March 31, 2000; 275(14): 10604 - 10610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Cerilli and M. R. Wick Fine Needle Aspiration Biopsies of the Head and Neck: The Surgical Pathologist's Perspective International Journal of Surgical Pathology, January 1, 2000; 8(1): 17 - 28. [Abstract] [PDF]
|
|
|
|
|
|
N. Montuori, F. Müller, S. De Riu, G. Fenzi, M. E. Sobel, G. Rossi, and M. Vitale Laminin Receptors in Differentiated Thyroid Tumors: Restricted Expression of the 67-Kilodalton Laminin Receptor in Follicular Carcinoma Cells J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2086 - 2092. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. Pötter, C. Bergwitz, and G. Brabant The Cadherin-Catenin System: Implications for Growth and Differentiation of Endocrine Tissues Endocr. Rev., April 1, 1999; 20(2): 207 - 239. [Abstract] [Full Text]
|
|
|
|
|
|
K. L. O'Connor, L. M. Shaw, and A. M. Mercurio Release of cAMP Gating by the {alpha}6{beta}4 Integrin Stimulates Lamellae Formation and the Chemotactic Migration of Invasive Carcinoma Cells J. Cell Biol., December 14, 1998; 143(6): 1749 - 1760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Takaoka, T. Yamada, M. Gotoh, Y. Kanai, K. Imai, and S. Hirohashi Cloning and Characterization of the Human beta 4-Integrin Gene Promoter and Enhancers J. Biol. Chem., December 11, 1998; 273(50): 33848 - 33855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Nawrocki, M. Polette, J. Van Hengel, J.-M. Tournier, F. Van Roy, and P. Birembaut Cytoplasmic Redistribution of E-Cadherin-Catenin Adhesion Complex Is Associated with Down-Regulated Tyrosine Phosphorylation of E-Cadherin in Human Bronchopulmonary Carcinomas Am. J. Pathol., November 1, 1998; 153(5): 1521 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Trusolino, G. Serini, G. Cecchini, C. Besati, F. S. Ambesi-Impiombato, P. C. Marchisio, and R. De Filippi Growth Factor-dependent Activation of {alpha}v{beta}3 Integrin in Normal Epithelial Cells: Implications for Tumor Invasion J. Cell Biol., August 24, 1998; 142(4): 1145 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Rabinovitz and A. M. Mercurio The Integrin {alpha}6{beta}4 Functions in Carcinoma Cell Migration on Laminin-1 by Mediating the Formation and Stabilization of Actin-containing Motility Structures J. Cell Biol., December 29, 1997; 139(7): 1873 - 1884. [Abstract] [Full Text] [PDF]
|
|