The 86-kD subunit of Ku autoantigen mediates homotypic and heterotypic adhesion of multiple myeloma cells

Journal of Clinical Investigation

Volumn 101, Issue 6, 1998, Pages 1379-1388

  Teoh, Gerrard ^a,b   Urashima, Mitsuyoshi ^a   Greenfield, Edward A ^a   Nguyen, Khuong A ^a   Lee, James F ^c   Chauhan, Dharminder ^a   Ogata, Atsushi ^a   Treon, Steven P ^a,d   Anderson, Kenneth C ^a,c  

^a HARVARD MEDICAL SCHOOL   (United States)

^b SINGAPORE GENERAL HOSPITAL   (Singapore)

^c DANA FARBER CANCER INSTITUTE   (United States)

^d MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

CD40; Cell membrane; DNA dependent protein kinase; IL 6; Ligands

Indexed keywords

AUTOANTIGEN; GLYCOPROTEIN GP 39; INTERLEUKIN 6; MONOCLONAL ANTIBODY; PROTEIN KINASE;

AMINO ACID SEQUENCE; ANIMAL CELL; ARTICLE; CANCER CELL; CANCER GROWTH; CELL ADHESION; CELL MEMBRANE; CELL SURVIVAL; HUMAN; HUMAN CELL; IMMUNOFLUORESCENCE; IMMUNOPRECIPITATION; MULTIPLE MYELOMA; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION;

3T3 CELLS; AMINO ACID SEQUENCE; ANIMALS; ANTIBODIES, BLOCKING; ANTIBODIES, MONOCLONAL; ANTIGENS, CD; ANTIGENS, CD40; ANTIGENS, NUCLEAR; AUTOANTIBODIES; BLOTTING, WESTERN; BONE MARROW CELLS; CD40 LIGAND; CELL ADHESION; CELL MEMBRANE; CELL NUCLEUS; CYTOPLASM; DNA HELICASES; DNA-BINDING PROTEINS; FIBRONECTINS; FLOW CYTOMETRY; HUMANS; INTERLEUKIN-6; MEMBRANE GLYCOPROTEINS; MICE; MICE, INBRED BALB C; MOLECULAR SEQUENCE DATA; MULTIPLE MYELOMA; NUCLEAR PROTEINS; PRECIPITIN TESTS; STROMAL CELLS; TRANSFECTION; TUMOR CELLS, CULTURED;

EID: 0032521131     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (62)

1. Ogata, A., and K.C. Anderson, 1996. Therapeutic strategies for inhibition of interleukin-6 mediated multiple myeloma cell growth. Leuk. Res. 20:303-307.
2. Ogata, A., D. Chauhan, G. Teoh, S.P. Treon, M. Urashima, R.L. Schlossman, and K.C. Anderson, 1997. IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J. Immunol. 159:2212-2221.
3. Chauhan, D., S. Kharbanda, A. Ogata. M. Urashima, G. Teoh, M. Robertson, D.W. Kufe, and K.C. Anderson. 1997. Interleukin-6 inhibits Fas-induced apoptosis and stress-activated protein kinase activation in multiple myeloma cells. Blood. 89:227-234.
4. Chauhan, D., P. Pandey, A. Ogata, G. Teoh, S. Treon, M. Urashima, S. Kharhanda, and K.C. Anderson. 1997. Dexamethasone induces apoptosis of multiple myeloma cells in a JNK/SAP kinase independent mechanism. Oncogene. 15:837-843.
5. Klein, B., and R. Bataille. 1992. Cytokine network in human multiple myeloma. Hematol. Oncol. Clin. N. Am. 6:273-284.
6. Rettig, M.B., H.J. Ma, R.A. Vescio, M. Põld, G. Schiller, D. Belson, A. Savage, C. Nishikubo, C. Wu, J. Fraser, el al. 1997. Kaposi's sarcoma-associated herpesvirus infection of bone marrow dendritic cells from multiple myeloma patients. Science. 276:1851-1854.
7. Westendorf. J., G. Ahmann. R. Armitage. M. Spriggs. J. Lust, P. Greipp, J. Kmtzmann, and D. Jelinek. 1994. CD40 expression in malignant plasma cells: role in stimulation of autocrine IL-6 secretion by a human myeloma cell line. J. Immunol. 152:117-128.
8. Urashima, M., D. Chauhan, M. Hatziyanni, A. Ogata, D. Hollenbaugh, A. Aruffo, and K.C. Anderson. 1996. CD40 ligand triggers interleukin-6 mediated B cell differentiation. Leuk. Res. 20:507-515.
9. Tong, A.W., B.-Q. Zhang, G. Mues, M. Solano, T. Hanson, and M.J. Stone. 1994. Anti-CD40 antibody binding modulates human multiple myeloma clonogenicity in vitro. Blood. 84:3026-3033.
10. Uchiyama, H., B.A. Barut, A.F. Mohrbacher, D. Chauhan, and K.C. Anderson. 1993. Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates IL-6 secretion. Blood. 82:3712-3720.
11. Lokhorst, H.M., T. Lamme, M. de Smet, S. Klein, R.A. de Weger, R. van Oers, and A.C. Bloem. 1994. Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term marrow cultures. Blood. 84:2269-2277.
12. Barille, S., M. Collette, R. Bataille, and M. Amiot. 1995. Myeloma cells upregulate interleukin-6 but downregulate osteocalcin production by osteoblastic cells through cell-to-cell contact. Blood. 86:3151-3159.
13. Chauhan, D., H. Uchiyama, Y. Akbarali, M. Urashima, K.I. Yamamoto, T.A. Libermann, and K.C. Anderson. 1996. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-κB. Blood. 87:1104-1112.
14. Urashima, M., A. Ogata, D. Chauhan, M. Hatziyanni, M.B. Vidriales, D.A. Dedera, R.L. Schlossman, and K.C. Anderson. 1996. Transforming growth factor β1: differential effects on multiple myeloma versus normal B cells. Blood. 87:1928-1938.
15. Uchiyama, H., B.A. Barut, D. Chauhan, S.A. Cannistra, and K.C. Anderson. 1992. Characterization of adhesion molecules on human myeloma cell lines. Blood. 80:2306-2314.
16. Pellat-Deceunynck, C., S. Barille, D. Puthier, M.J. Rapp, J.L. Harousseau, R. Bataille, and M. Amiot. 1995. Adhesion molecules on human myeloma cells: significant changes in expression related to malignancy, tumor spreading and immortalization. Cancer Ras. 55:3647-3653.
17. Teoh, G., and K.C. Anderson. 1997. Interaction of tumor and host cells with adhesion and extracellular matrix molecules in the development of multiple myeloma. Hematol. Oncol. Clin. N. Am. 11:27-12.
18. Urashima, M., B.P. Chen, S. Chen, G.S. Pinkus, R.T. Bronson, D.A. Dedera, Y. Hoshi, G. Teoh, A. Ogata, S.P. Treon, et al. 1997. The development of a model for the homing of multiple myeloma cells to human bone marrow. Blood. 90:754-765.
19. Mimori, T., M. Akizuki, H. Yamagata, S. Inada, S. Yoshida, and M. Homma. 1981. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J. Clin. Invest. 68:611-620.
20. Smider, V., W.K. Rathmell, M.R. Lieber, and G. Chu. 1994. Restoration of x-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science. 266:288-291.
21. Bouhnov, N.V., K.T. Hall, Z. Wills, S.E. Lee, D.M. He, D.M. Benjamin, C.R. Pulaski, H. Band, W. Reeves, E.A. Hendrickson, and D.T. Weaver. 1995. Complementation of the ionizing radiation sensitivity. DNA end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen. Proc. Natl. Acad. Sci. USA. 92:890-894.
22. Liang, F., and M. Jasin. 1996. Ku80-deficient cells exhibit excess degradation of extrachromosomal DNA. J. Biol. Chem. 271:14405-14411.
23. Liang, F., P.J. Romanienko, D.T. Weaver, P.A. Jeggo, and M. Jasin. 1996. Chromosomal double-strand break repair in Ku80-deficient cells. Proc. Natl. Acad. Sci. USA. 93:8929-8933.
24. Grawunder, U., N. Finnie, S.P. Jackson, B. Riwar, and R. Jessberger. 1996. Expression of DNA-dependent protein kinase holoenzyme upon induction of lymphocyte differentiation and V(D)J recombination. Eur. J. Biochem. 241:931-940.
25. Aizawa, S., M. Yaguchi, M. Nakao, K. Toyama, S. Inokuchi, T. Imai, M. Uasuda, R. Nabeshima, and H. Hanada. 1994. Hematopoietic supportive function of human bone marrow stromal cell lines established by a recombinant SV40-adenovirus vector. Exp. Hematol. 22:482-487.
26. Kohler, G., and C. Milstein. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 256:495-497.
27. Kearney, J.F., A. Radbruch, B. Liesegang, and K. Rajewsky. 1979. A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J. Immunol. 123: 1548-1550.
28. Rothlein, R., and T.A. Springer. 1986. The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester. J. Exp. Med. 163:1132-1149.
29. Chauhan, D., S. Kharbanda, H. Uchiyama, M. Urashima, J. Sen, R. Fuguso, D.W. Kufe, and K.C. Anderson. 1994. Identification of upstream signals regulating interleukin-6 gene expression during in vitro treatment of human B cells with pokeweed milogen. Blood. 84:2243-2252.
30. Fernandez, J., L. Andrews, and S.M. Mische. 1994. A one-step enzymatic digestion procedure tor PVDF-bound proteins that does not require PVP-40. In Techniques in Protein Chemistry V. J.W. Crabb, editor. Academic Press. Inc., San Diego, CA. 215-222.
31. Yaneva, M., R. Ochs, D.K. McRorie, S. Zweig, and H. Busch. 1985. Purification of an 86-70 kD nuclear DNA-associated protein complex. Biochim. Biophys. Acta. 841:22-29.
32. Reeves, W.H. 1985. Use of monoclonal antibodies for the characterization of novel DNA-binding proteins recognized by human autoimmune sera. J. Exp. Med. 161:18-39.
33. Yaneva, M., and H. Busch. 1986. A 10S particle released from deoxyri-bonuclease-sensitive regions of HeLa cell nuclei contains the 86-kilodalton-70-kilodalton protein complex. Biochemistry. 25:5057-5063.
34. Reeves, W.H., and Z.M. Sthoeger. 1989. Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen. J. Biol. Chem. 264:5047-5052.
35. Mimori, T., Y. Ohosone, N. Hama, A. Suwa, M. Akizuki, M. Homina, A.J. Griffith, and J.A. Hardin. 1990. Isolation and characterization of cDNA encoding the 80-kD subunit protein of the human autoantigen Ku (p70/p80) recognized by autoantibodies from patients with scleroderma-polymyositis overlap syndrome. Proc Natl. Acad. Sci. USA. 87:1777-1781.
36. Allaway, G.P., A.A. Vivino, L.D. Kohn, A.L. Notkins, and B.S. Prabhakar. 1990. Characterization of the 70kD component of the human Ku autoantigen expressed in insect cell nuclei using a recombinant baculovirus vector. Biochem. Biophys. Res. Commun. 168:747-755.
37. Porges, A.J., T. Ng, and W.H. Reeves. 1990. Antigenic determinants of the Ku (p70/p80) autoantigen are poorly conserved between species. J. Immunol. 145:4222-4228.
38. Gottleib, T.M., and S.P. Jackson. 1993. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 72:131-142.
39. Lees-Miller, S.P., Y.-R. Chen, and C.W. Anderson. 1990. Human cells contain a DNA-activated protein kinase that phosphorylates simian virus 40 T antigen, mouse p53. and the human Ku autoantigen. Mol. Cell. Biol. 10:6472-6481.
40. Anderson, C.W., and S.P. Lees-Miller. 1992. The nuclear serine/threonine protein kinase DNA-PK. Crit. Rev. Eukaryotic Gene Expr. 2:283-314.
41. Hoff, C.M., A.K. Ghosh, B.S. Prabhakar, and S.T. Jacob. 1994. Enhancer 1 binding factor, a Ku-related protein, is a positive regulator of RNA polymerasc I transcription initiation. Proc. Natl. Acad. Sci. USA. 91:762-766.
42. Okumura, K., S. Takagi, G. Sakaguchi, K. Naito, N. Minoura-Tada, H. Kobayashi, T. Mimori, Y. Hinuma, and H. Igarashi, 1994. Autoantigen Ku protein is involved in DNA binding proteins which recognize the U5 repressive element of human T-cell leukemia virus type I long terminal repeat. FEBS Lett. 382:94-100.
43. Genersch, E., C. Eckerskorn, F. Lottspeich, C. Herzog, K. Kühn, and E. Pösehl. 1995. Purification of the sequence-specific transcription factor CTCBF. involved in the control of human collagen IV genes: subunits with homology to Ku antigen. EMBO (Eur. Mol. Biol. Organ.) J. 14:791-800.
44. Niu, H., J. Zhang, and S.T. Jacob. 1995. E1BF/Ku interacts physically and functionally with the core promoter binding factor CPBF and promotes the basal transcription of rat and human ribosumal RNA genes. Gene Expr. 4:111-124.
45. Giffin. W., H. Torrance, D.J. Rodda, G.G. Préfontaine, L. Pope, and R.J.G. Haché. 1996. Sequence-specific DNA binding by Ku autoantigen and its effects on transcription. Nature. 380:265-268.
46. Tuteja, N., R. Tuteja, A. Ochem, P. Taneja, N.W. Huang, A. Simoncsits. S. Susic, K. Rahmnn, L. Marusic. J. Chen. et al. 1994. Human DNA helicase II: a novel DNA unwinding enzyme identified as the Ku autoantigen. EMBO (Eur. Mol. Biol. Organ.) J. 13:4991-5001.
47. Dvir, A., S.R. Peterson, M.W. Knuth, H. Lu, and W.S. Dynan. 1992. Ku autoantigen is the regulatory component of a template-associated protein kinase that phosphorylates RNA polymerase II. Proc. Natl. Acad. Sci. USA. 89: 11920-11924.
48. Kaczmarski, W., and S.A. Khan. 1993. Lupus autoantigen Ku protein binds HIV-1 TAR RNA in vitro. Biochem. Biopliys. Res. Commun. 196:935-942.
49. Porter, S.E., P.W. Greenwell, K.B. Ritchie, and T.D. Petes. 1996. The DNA-binding protein Hdflp (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucl. Acids Res. 24:582-585.
50. Messier, H., T. Fuller, S. Mangal, H. Brickner, S. Igarashi, J. Gaikwad, R. Fotedar, and A. Fotedar. 1993. p70 lupus autoantigen binds the enhancer of the T-cell receptor β-chain gene. Proc. Natl. Acad. Sci. USA. 90:2685-2689.
51. Prabhakar, B.S., G.P. Allaway, J. Srinivasappa, and A.L. Notkins. 1990. Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen. J. Clin. Invest. 86:1301-1305.
52. Hong, T.J., J. Escribano, and M. Coca-Prados. 1994. Isolation of cDNA clones encoding the 80-kd subunit protein of the human autoantigen Ku (p70/ p80) by antisera raised against ciliary processes of human eye donors. Invest. Ophthalmol. Vis. Sci. 35:4023-4030.
53. Chan, J.Y., M.I. Lerman, B.S. Prabhakar, O. Isozaki, P. Santisteban, R.C. Kuppers, E.L. Oates, A.L. Notkins, and L.D. Kohn. 1989. Cloning and characterization of a cDNA that encodes a 70-kD novel human thyroid autoantigen. J. Biol. Chem. 264:3651-3654.
54. Le Romancer, M., Y. Cherifi, F. Reyl-Desmars, and M.J.M. Lewin. 1993. Somatostatin specifically binds p86 suhunit of the autoantigen Ku. C. R. Acad. Sci. Paris. 316:1283-1285.
55. Le Romancer, M., F. Reyl-Desmars, Y. Cerifi, C. Pigeon, S. Bottari, O. Meyer, and M.J.M. Lewin. 1994. The 86-kD subunit of autoantigen Ku is a somatostatin receptor regulating protein phosphatase-2A activity. J. Biol. Chem. 296:17464-17468.
56. Hartley, K.O., D. Gell. G.C.M. Graeme, H. Zhang, N. Divecha, M.A. Connelly, A. Admon, S.P. Lees-Miller, and C.W. Anderson. 1995. DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell. 82:849-856.
57. Bakkus, M.H.C., I. van Riet, B. Van Camp, and K. Thielemann. 1994. Evidence that the clonogenic cell in multiple myeloma originates from a preswitched but somatically mutated B cell. Br. J. Haemtol. 87:68-74.
58. Zelazowski, P., E.E. Max, M.R. Kehry, and C.M. Snapper. 1997. Regulation of Ku expression in normal murine B cells by stimuli that promote switch recombination. J. Immunol. 159:2559-2562.
59. Ouyang, H., A. Nussenzweig, A. Kurimasa, V.D.C. Soares, X. Li, C. Cordon-Cardo, W.-H. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination in vivo. J. Exp. Med. 186:921-929.
60. Nussenzweig, A., C. Chen, V.D.C. Soares, M. Sanchez, K. Sokol, M.C. Nussenzweig, and G.C. Li. 1997. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature. 382:551-555.
61. Pilarski, L.M., and A.J. Belch. 1994. Circulating monoclonal B cells expressing p-glycoprotein may be a reservoir of multidrug resistant disease in multiple myeloma. Blood. 83:724-736.
62. Yaneva, M., and F.C. Arnett. 1989. Autoantibodies against Ku protein in sera from patients with autoimmune diseases. Clin. Exp. Immunol. 76:366-372.