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Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo 104 [Yut. S., Se. H., M. N., Yuk. S.]; Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 [Yut. S., O. A.]; and Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606 [Sh. H., M. T.], Japan
Two distinct calcium-sensitive cell-cell adhesion molecules were identified in human epithelial tissues and carcinomas using two monoclonal antibodies raised against vulvar epidermoid carcinoma A-431 and human mammary carcinoma MCF-7 and selected on the basis of their activities to disrupt cell-cell adhesion. In immunoblot analysis, these antibodies, designated NCC-CAD-299 and HECD-1, detected main bands of Mr 118,000 and 124,000, respectively. Purified tryptic fragments of the antigen recognized by NCC-CAD-299 showed cross-reactivity with a rabbit antiserum against mouse P-cadherin, indicating that this molecule was the human homologue of P-cadherin. On the other hand, the antigen recognized by HECD-1 showed essentially the same tissue distribution pattern as E-cadherin in the mouse, suggesting that this molecule is the human homologue of E-cadherin. Availability of these monoclonal antibodies to human P- and E-cadherin allowed us to examine their distributions in human tissues immunohistochemically. Both antigens were detected in epithelial tissues, but they showed distributions that were distinct from each other. The antigen recognized by HECD-1 was expressed in almost all epithelial tissues, while distribution of the other one recognized by NCC-CAD-299 was restricted to the basal or lower layers of stratified epithelia in which both antigens were coexpressed. Moreover, immunohistochemical examination of 44 lung carcinomas showed that both molecules were coexpressed in all of them, and suggested that expression of P-cadherin was closely related to the differentiation of carcinoma cells.
1 This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare of Japan for a Comprehensive 10-Year Strategy for Cancer Control.
2 Awardee of Research Resident Fellowship from the Foundation for Promotion of Cancer Research.
3 To whom reprint requests should be addressed.
Received 9/ 8/88. Revised 12/30/88. Accepted 1/20/89.
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I. Kitajima, K. Kawahara, N. Hanyu, H. Shin, T. Tokioka, Y. Soejima, J. Tsutsui, M. Ozawa, T. Shimayama, and I. Maruyama Enhanced E-cadherin expression and increased calcium-dependent cell-cell adhesion in human T-cell leukemia virus type I Tax-expressing PC12 cells J. Cell Sci., March 1, 1996; 109(3): 609 - 617. [Abstract] [PDF]
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A. Zhu and F. Watt Expression of a dominant negative cadherin mutant inhibits proliferation and stimulates terminal differentiation of human epidermal keratinocytes J. Cell Sci., January 12, 1996; 109(13): 3013 - 3023. [Abstract] [PDF]
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S. Byers, C. Sommers, B Hoxter, A. Mercurio, and A Tozeren Role of E-cadherin in the response of tumor cell aggregates to lymphatic, venous and arterial flow: measurement of cell-cell adhesion strength J. Cell Sci., January 5, 1995; 108(5): 2053 - 2064. [Abstract] [PDF]
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M Rabino, L Trusolino, M Prat, O Cremona, P Savoia, and P. Marchisio A monoclonal antibody identifies a novel GPI-anchored glycoprotein involved in epithelial intercellular adhesion J. Cell Sci., January 6, 1994; 107(6): 1413 - 1428. [Abstract] [PDF]
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A Tang, M. Eller, M Hara, M Yaar, S Hirohashi, and B. Gilchrest E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro J. Cell Sci., January 4, 1994; 107(4): 983 - 992. [Abstract] [PDF]
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L. Su, B Vogelstein, and K. Kinzler Association of the APC tumor suppressor protein with catenins Science, December 10, 1993; 262(5140): 1734 - 1737. [Abstract] [PDF]
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M Fabre and A Garcia de Herreros Phorbol ester-induced scattering of HT-29 human intestinal cancer cells is associated with down-modulation of E-cadherin J. Cell Sci., January 10, 1993; 106(2): 513 - 521. [Abstract] [PDF]
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P Navarro, E Lozano, and A Cano Expression of E- or P-cadherin is not sufficient to modify the morphology and the tumorigenic behavior of murine spindle carcinoma cells. Possible involvement of plakoglobin J. Cell Sci., January 8, 1993; 105(4): 923 - 934. [Abstract] [PDF]
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J Baker and D Garrod Epithelial cells retain junctions during mitosis J. Cell Sci., January 2, 1993; 104(2): 415 - 425. [Abstract] [PDF]
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M Takeichi Cadherin cell adhesion receptors as a morphogenetic regulator Science, March 22, 1991; 251(5000): 1451 - 1455. [Abstract] [PDF]
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Y. Ino, M. Gotoh, M. Sakamoto, K. Tsukagoshi, and S. Hirohashi Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis PNAS, January 8, 2002; 99(1): 365 - 370. [Abstract] [Full Text] [PDF]
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