Abstract
KAI1 is a metastasis suppressor gene for human prostate cancer. To reveal the effect of KAI1 on the in vivo metastasis of tumors other than prostatic cancer, we transfected a human KAI1 cDNA into highly metastatic B16‐BL6 murine melanoma cells and established stable transfectant clones with different expression levels of KAI1 message. The following results were obtained with the use of those transfectants. (1) Cell aggregation assay revealed a significantly enhanced Ca2+‐independent aggregation of B16‐BL6 cells by KAI1 cDNA transfection compared with mock transfectants (P<0.01). (2) The in vivo phagokinetic activity and invasive ability of KAI1 transfectants were clearly decreased as compared with those of mock transfectants (P<0.01). There was no significant effect of KAI1 expression on the in vitro or in vivo proliferation of B16‐BL6 cells. (3) Lung colony formation of intravenously injected KAI1 transfectants in nude mice was significantly reduced as compared with mock transfectants or parental B16‐BL6 cells (P<0.01). These data suggest that KAI1 expression gives rise to the suppression of invasive and metastatic potentials of B16‐BL6 cells.
Keywords: KAI1 gene, Invasion, Metastasis, Cell adhesion
Full Text
The Full Text of this article is available as a PDF (297.8 KB).
REFERENCES
- 1. ) Dong , J. T. , Lamb , P. W. , Rinker‐Schaeffer , C. W. , Vukanovic , J. , Ichikawa , T. , Isaacs , J. T. and Barrett , J. C.KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2 . Science , 268 , 884 – 886 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Ueda , T. , Ichikawa , T. , Tamura , J. , Mikata , A. , Akakura , K. , Akimoto , S. , Imai , T. , Yoshie , O. , Shiraishi , T. , Yatani , R. , Ito , H. and Shimazaki , J.Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer . Am. J. Pathol. , 149 , 1435 – 1440 ( 1996. ). [PMC free article] [PubMed] [Google Scholar]
- 3. ) Boucheix , C. , Benoit , P. , Frachet , P. , Billard , M. , Worthington , R. E. , Gagnon , J. and Uzan , G.Molecular cloning of the CD9 antigen: a new family of cell surface proteins . J. Biol. Chem. , 266 , 117 – 122 ( 1991. ). [PubMed] [Google Scholar]
- 4. ) Horejsi , V. and Vlcek , C.Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63 (review) . FEBS Lett. , 288 , 1 – 4 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Gil , L. M. , Vita , N. , Lebel‐Binay , S. , Miloux , B. , Chalon , P. , Kaghad , M. , Marchiol‐Fournigaul , C. , Conjeaud , H. , Caput , D. , Ferrara , P. , Fradelizi , D. and Quillet‐Mary , A.A member of the tetra spans transmembrane protein superfamily is recognized by a monoclonal antibody raised against an HLA class I‐deficient, lymphokine‐activated killer‐susceptible, B lymphocyte line . J. Immunol. , 148 , 2826 – 2833 ( 1992. ). [PubMed] [Google Scholar]
- 6. ) Wright , M. D. and Tomlinson , M. G.The ins and outs of the transmembrane 4 superfamily . Immunol. Today , 15 , 588 – 594 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Gaugitsch , H. W. , Hofer , E. , Huber , N. E. , Schnabl , E. and Baumruker , T.A new superfamily of lymphoid and melanoma cell proteins with extensive homology to Schistosoma mansoni antigen Sm23 . Eur. J. Immunol. , 21 , 377 – 383 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Fukudome , K. , Furuse , M. , Imai , T. , Nishimura , M. , Takagi , S. , Hinuma , Y. and Yoshie , O.Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T‐cell leukemia virus type 1 of C33 antigen in HTLV‐1‐positive T cells . J. Virol. , 66 , 1394 – 1401 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) Imai , T. , Fukudome , K. , Takagi , S. , Nagira , M. , Furuse , M. , Fukuhara , N. , Nishimura , M. , Hinuma , Y. and Yoshie , O.C33 antigen recognized by monoclonal antibodies inhibitory to human T cell leukemia virus type 1‐induced syncytium formation is a member of a new family of trans‐membrane proteins including CD9, CD37, CD53, and CD63 . J. Immunol. , 149 , 2879 – 2886 ( 1992. ). [PubMed] [Google Scholar]
- 10. ) Nojima , Y. , Hirose , T. , Tachibana , K. , Tanaka , T. , Shi , L. , Doshen , J. , Freeman , G. J. , Schlossman , S. F. and Morimoto , C.The 4F9 antigen is a member of the tetra spans transmembrane protein family and functions as an accessory molecule in T cell activation and adhesion . Cell. Immunol. , 152 , 249 – 260 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Boucheix , C. , Benoit , P. , Frachet , P. , Billard , M. , Worthington , R. E. , Gagnon , J. and Uzan , G.Molecular cloning of the CD9 antigen: a new family of cell surface proteins . J. Biol. Chem. , 266 , 117 – 122 ( 1991. ). [PubMed] [Google Scholar]
- 12. ) Oren , R. , Takahashi , S. , Doss , C. , Levy , R. and Levy , S.TAPA‐1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins . Mol. Cell. Biol. , 10 , 4007 – 4015 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. ) Imai , T. and Yoshie , O.C33 antigen and M38 antigen recognized by monoclonal antibodies inhibitory to syncytium formation by human T cell leukemia virus type 1 are both members of the transmembrane 4 superfamily and associate with each other and with CD4 or CD8 in T cells . J. Immunol. , 151 , 6470 – 6481 ( 1993. ). [PubMed] [Google Scholar]
- 14. ) Saiki , R. K. , Scharf , S. , Faloona , F. , Mullis , K. B. , Horn , G. T. , Erlich , H. and Arnheim , N.Enzymatic amplification of β‐globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia . Science , 230 , 1350 – 1354 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Takaoka , A. , Adachi , M. , Okuda , H. , Sato , S. , Yawata , A. , Hinoda , Y. , Takayama , S. , Reed , J. C. and Imai , K.Anticell death activity promotes pulmonary metastasis of melanoma cells . Oncogene , 14 , 2971 – 2977 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Rojas , M. , Fuks , A. and Stanners , C. P.Biliary glycoprotein, a member of the immunoglobulin supergene family, functions in vitro as a Ca++‐dependent intercellular adhesion molecule . Cell Growth Differ , 1 , 527 – 533 ( 1990. ). [PubMed] [Google Scholar]
- 17. ) Albrecht‐Buehler , G.The phagokinetic tracks of 3T3 cells . Cell , 11 , 359 – 404 ( 1977. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Albini , A. , Iwamoto , Y. , Kleinman , H. K. , Martin , G. R. , Aaronson , S. A. , Kozlowski J. M. and McEwan , R. N.A rapid in vitro assay for quantitating the invasive potential of tumor cells . Cancer Res. , 47 , 3239 – 3245 ( 1987. ). [PubMed] [Google Scholar]
- 19. ) Repesh , L. A.A new in vitro assay for quantitating tumor cell invasion . Invasion Metastasis , 9 , 192 – 196 ( 1989. ). [PubMed] [Google Scholar]
- 20. ) Parish , C. R. , Jakobsen , K. B. and Coombe , D. R.A basement membrane permeability assay which correlates with the metastatic potential of tumour cells . Int. J. Cancer , 52 , 378 – 383 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Mosmann , T.Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxocity assays . J. Immunol. Methods , 65 , 55 – 63 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Tada , H. , Shiho , O. , Kuroshima , K. , Koyama , M. and Tsukamoto , K.An improved colorimetric assay for interleukin‐2 . J. Immunol. Methods , 93 , 157 – 165 , ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Leone , A. , Flatow , U. , King , C. E. , Sandeen , M. A. , Margulies , M. K. , Liotta , L. A. and Steeg , P. S.Reduced tumor incidence, metastatic potential and cytokine responsiveness of nm 23‐transfected melanoma cells . Cell , 65 , 25 – 35 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Adachi , M. , Taki , T. , Ieki , Y. , Huang , C. L. , Higashiyama , M. and Miyake , M.Correlation of KAI1/CD82 gene expression with good prognosis in patients with non‐small cell lung cancer . Cancer Res. , 56 , 1751 – 1755 ( 1996. ). [PubMed] [Google Scholar]
- 25. ) Guo , X. , Friess , H. , Graber , H. U. , Kashiwagi , M. , Zimmermann , A. , Korc , M. and Buhler , M. W.KAI1 expression is up‐regulated in early pancreatic cancer and decreased in the presence of metastases . Cancer Res. , 56 , 4876 – 4880 ( 1996. ). [PubMed] [Google Scholar]