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Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in renal cell carcinoma

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Abstract

Intercellular adhesion molecule-1 (ICAM-1) mediates two important functional. aspects of tumor biology, namely enhancement of tumor metastasis and mediation of host defense mechanisms such as lymphocyte-mediated tumor cytotoxicity. Since ICAM-1 is expressed by most renal cell carcinomas (RCC), the regulation of ICAM-1 expression is important in understanding the biological behavior of RCC. We report an investigation on ICAM-1 expression and molecular regulation by cytokines and protein kinase C activator on RCC cell lines. Of the various cytokines, tumor necrosis factor αa (TNFα), interferon-γ (IFNγ), and phorbol myristate acetate (PMA) strongly upregulated ICAM-1 protein expression on RCC. The kinetics of ICAM-1 message induction was studied by Northern analysis of total RNA extracted from RCC and normal kidney proximal tubular (NKPT) cells. Time course studies showed that ICAM-1 mRNA was upregulated by INFγ, TNFα, and PMA, plateaued after 2 h, and remained increased for up to 24 h. Although ICAM-1 mRNA in NKPT cells was upregulated by these cytokines, their messages returned to basal levels after 24 h. ICAM-1 mRNA stability assays showed that both unstimulated and stimulated RCC cells had very stable ICAM-1 mRNA up to 24 h. In order to investigate whether increased gene transcription contributes to ICAM-1 upregulation, RCC cells were treated with TNFα, IFNγ, or PMA with or without simultaneous addition of actinomycin D. ICAM-1 message induction-blocking studies suggested that primary upregulation of ICAM-1 mRNA may be caused by transcriptional upregulation. These results suggest that long-lasting ICAM-1 message upregulation in response to cytokines or PMA may be due to transcriptional upregulation in the early phase and stabilization of ICAM-1 message in the later phase (after 4 h). These observations suggest that RCC may lack the normal downregulatory mechanisms which control ICAM-1 expression and may explain the high frequency of ICAM-1 expression observed on primary human RCC.

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References

  1. Becker JC, Dummer R, Hartmann AA, Burg G, Schmidt RE (1991) Shedding of ICAM-1 from human melanoma cell lines induced by IFN-γ and tumor necrosis factor-α. J Immunol 147:4398

    Google Scholar 

  2. Belldegrum A, Muul LM, Rosenberg SA (1998) Interleukin 2 expanded tumor-infiltrating lymphocytes in human renal cell cancer: Isolation, characterization, and antitumor activity. Cancer Res 48:206

    Google Scholar 

  3. Bigler CF, Norris D, Weston WL, Arend WP (1992) Interleukin-1 receptor antagonist production by human keratinocytes. J Invest Dermatol 98:38

    Google Scholar 

  4. Billaud M, Calender A, Seigneurin J-M, Lenoir GM (1987) LFA-1, LFA-3, and ICAM-1 expression in Burkitt's lymphoma. Lancet i:1327

    Google Scholar 

  5. Bohjanen PR, Betryniak B, June CH, Thompson CB, Lindsten T (1991) An inducible cytoplasmic factor (AU-B) binds selectively to AUUUA multimers in 3′ untranslated region of lymphokine mRNA. Mol Cell Biol 11:3288

    Google Scholar 

  6. Boyd AW, Wawryk SO, Burns GF, Fecondo JV (1988) Intercellular adhesion molecule 1 (ICAM-1) has a central role in cellcell contact-mediated immune mechanisms. Proc Nat] Acad Sci USA 85:3095

    Google Scholar 

  7. Budd GT, Osgood B, Barna B, Boyett JM, Finke J, Medendorp SV, Murthy S, Novak C, Sergi J, Tubbs R, Bukowski RM (1989) Phase I clinical trial of interleukin 2 and a-interferon: Toxicity and immunologic effects. Cancer Res 49:6432

    Google Scholar 

  8. Busson P, Zhang Q, Guillon J-M, Gregory CD, Young LS, Clausse B, Lipinski M, Rickinson AB, Tursz T (1992) Elevated expression of ICAM1 (CD54) and minimal expression of LFA3 (CD58) in Epstein-Barr-virus-positive nasopharyngeal carcinoma cells. Int J Cancer 50:863

    Google Scholar 

  9. Campbell SC, Tanabe K, Alexnder JP, Edinger M, Tubbs RR, Klein EA (1994) Intercellular adhesion molecule-1 expression by bladder cancer cells: functional effects. J Urol 151:1385

    Google Scholar 

  10. Cleveland DW, Yen TJ (1989) Multiple determinants of eukaryotic mRNA stability. New Biol 1:121

    Google Scholar 

  11. Desroches CV, Rigal D, Andreoni, C (1991) Regulation and functional involvement of distinct determinants of leukocyte function-associated antigen 1 (LFA-1) in T-cell activation in vitro. Scand J Immunol 33:277

    Google Scholar 

  12. Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA (1986) Induction by IL 1 and interferon-γ: Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 137:245

    Google Scholar 

  13. Ebert T, Bander NH, Finstad CL, Ramsawak RD, Old LJ (1990) Establishment and characterization of human renal cancer and normal kidney cell lines. Cancer Res 50:5531

    Google Scholar 

  14. Fady G, Gardner AM, Gera JF, Lichtenstein A (1992) Interferon-induced increase in sensitivity of ovarian cancer targets to lysis by lymphokine-activated killer cells: Selective effects on HER 2/neu-overexpressing cells. Cancer Res 52:764

    Google Scholar 

  15. Gerritsen ME, Kelley KA, Ligon G, Perry CA, Shen C, Szczepanski A, Carley WW (1993) Regulation of the expression of intercellular adhesion molecule 1 in cultured human endothelial cells derived from rheumatoid synovium. Arthritis Rheum 36:593

    Google Scholar 

  16. Grant AJ, Merchant RE, Hall RE (1989) Interleukin-2 modulates the expression of lymphocyte function-associated antigen-one (LFA-1) and p150,95 during the generation of lymphokine-activated killer (LAK) cells. Immunology 66:117

    Google Scholar 

  17. Gregory CD, Murray RJ, Edwards CF, Rickinson AB (1988) Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance. J Exp Med 167:1811

    Google Scholar 

  18. Hashimura T, Tubbs RR, Connelly R, Caulfield MJ, Trindade CS, McMahon JT, Galetti TP, Edinger M, Sandberg AA, Cin PD, Sait SJ, Pontes JE (1989) Characterization of two cell lines with distinct phenotypes and genotypes established from a patient with renal cell carcinoma. Cancer Res 49:7064

    Google Scholar 

  19. Hildreth JEK, Gotch FM, Hildreth PDK, McMichael AJ (1983) A human lymphocyte-associated antigen involved in cellmediated lympholysis. Eur J Immunol 13:202

    Google Scholar 

  20. Jackson AM, Alexandrov AB, Prescott S, James K, Chisholm, GD (1992) Role of adhesion molecule in lymphokine-activated killer cell killing of bladder cancer cells: further evidence for a third ligand for leukocyte function-associated antigen-1. Immunology 76:286

    Google Scholar 

  21. Jevnikar AM, Wuthrich RP, Takei F, Xu H, Brennan DC, Glimcher LH, Rubin-Kelley VE (1990) Differing regulation and function of ICAM-1 and class II antigens on renal tubular cells. Kidney Int 38:417

    Google Scholar 

  22. Johnson JP, Stade BG, Holzmann B, Schwable W, Riethmuller G (1989) De novo expression of intercellular-adhesion molecule 1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci USA 86:641

    Google Scholar 

  23. Kradin RL, Lazarus DS, Dubinett SM, Gifford J, Grove B, Kurnick JT, Pretter FI, Pinto CE, Davison E, Collahan RJ, Strauss HW (1989) Tumor-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Lancet i:577

    Google Scholar 

  24. Kuijpers KC, Kuijpers TW, Zeijlemaker WP, Lucas CJ, van Lier RAW, Miedema F (1990) Analysis of the role of leukocyte function-associated antigen-1 in activation of human influenza virus-specific T cell clones. J Immunol 144:3281

    Google Scholar 

  25. Kuppner MC, Van Meir E, Hamou MF, De Tribolet N (1990) Cytokine regulation of intercellular adhesion molecule-1 (ICAM-1) expression on human glioblastoma cells. Clin Exp Immunol 81:142

    Google Scholar 

  26. Lanier LL, Loken MR (1984) Human lymphocyte subpopulations identified by using three-color immunofluorescence and flow cytometry analysis: Correlation of Leu-2, Leu-3, Leu-3, Leu-7, Leu-8, and Leu-11 cell surface antigen expression. J Immunol 132:151

    Google Scholar 

  27. Makgoba MW, Sanders ME, Luce GEG, Dustin ML, Springer TA, Clark EA, Mannoni P, Shaw S (1988) ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature 331:86

    Google Scholar 

  28. Makgoba MW, Sanders ME, Luce GEG, Gugel EA, Dustin ML, Springer TA, Shaw S (1988) Functional evidence that intercellular adhesion molecule-1 (ICAM-1) is a ligand for LFA 1-dependent adhesion in T cell-mediated cytotoxicity. Eur J Immunol 18:637

    Google Scholar 

  29. Myers CL, Desai SN, Schembri-King J, Letts GL, Wallace RW (1992) Discriminatory effects of protein kinase inhibitors and calcium ionophore on endothelial ICAM-1 induction. Am J Physiol 262:0365

    Google Scholar 

  30. Naganuma H, Kiessling R, Patarroyo M, Hansson M, Handgretinger R, Gronberg A (1991) Increased susceptibility of IFNy treated neuroblastoma cells to lysis by lymphokine-activated killer cells: Participation of ICAM-1 induction of target cells. Int J Cancer 47:527

    Google Scholar 

  31. Natali P, Nicotra MR, Cavaliere R, Bigotti A, Romano G, Temponi M, Ferrone SD (1990) Differential expression of intercellular adhesion molecule 1 in primary and metastatic melanoma lesion. Cancer Res 50:1271

    Google Scholar 

  32. Pandolfi F, Trentin L, Boyle LA, Stamenkovic I, Byers HR, Colvin RB, Kurnik JT (1992) Expression of cell adhesion molecules in human melanoma cell lines and their role in cytotoxicity mediated by tumor-infiltrating lymphocytes. Cancer 69:1165

    Google Scholar 

  33. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, White DE (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316:889

    Google Scholar 

  34. Rothlein R, Czajkowski M, O'Neill MM, Marlin SD, Mainolfi E, Merluzzi VJ (1988) Induction of intercellular adhesion molecule 1 on primary and continuous cell lines by pro-inflammatory cytokines. Regulation by pharmacologic agents and neutralizing antibodies. J Immunol 141:1665

    Google Scholar 

  35. Sanchez-Madrid F, Krensky AM, Ware CF, Robbins E, Strominger JL, Burakoff, SJ, Springer TA (1982) Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci USA 79:7489

    Google Scholar 

  36. Shaw G, Kamen R (1986) A conserved AU sequence from the 3′ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46:659

    Google Scholar 

  37. Sin G, Hedrick SM, Brian AA (1989) Isolation of the marine intercellular adhesion molecule 1 (ICAM-1) gene. ICAM-1 enhances antigen-specific T cell activation. J. Immunol 143:3813

    Google Scholar 

  38. Springer TA (1990) Adhesion receptors of the immune system. Nature 346:425

    Google Scholar 

  39. Stauder R, Greil R, Schulz TF, Thaler J, Gattringer C, Radaskiewicz T, Dierich MP, Huber H (1989) Expression of leukocyte function-associated antigen-1 and 7F7-antigen, an adhesion molecule related to intercellular adhesion molecule-1 (ICAM-1) in non-Hodgkin lymphomas and leukaemias: Possible influence on growth pattern and leukaemic behaviour. Clin Exp Immunol 77:234

    Google Scholar 

  40. Stanton DE, Marlin SD, Stratowa C, Dustin ML, Springer TA (1988) Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52:925

    Google Scholar 

  41. Tanabe K, Alexander JP, Connelly R, Edinger M, Tubbs RR, Finke JH, Novick AC, Klein EA (1996) The expression of CD44 and CD54 by renal cell carcinoma and their role in cytolysis mediated by autologous tumor infiltrating lymphocytes (TIL) and in IL2 dependent TIL proliferation. (submitted)

  42. Tomita Y, Nishiyama T, Watanabe H, Fujiwara M, Sato S (1990) Expression of intercellular adhesion molecule-1 (ICAM-1) on renal-cell cancer: Possible significance in host immune responses. Int J Cancer 46:1001

    Google Scholar 

  43. Vanky F, Wang P, Patarroyo M, Klein E (1990) Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumor cells is required for their interaction with autologous lymphocytes in vitro. Cancer Immunol Immunother 31:19

    Google Scholar 

  44. Vogetseder W, Feichtinger H, Schulz TF, Schwaeble W, Tabaczewski P, Mitterer M, Bock G, Marth C, Dapunt O, Mikuz G, Dierich MP (1989) Expression of 7F7-antigen, a human adhesion molecule identical to intercellular adhesion molecule-1 (ICAM-1) in human carcinomas and their stromal fibroblasts. Int J Cancer 43:768

    Google Scholar 

  45. Wertheimer SJ, Myers CL, Wallace RW, Parks TP (1992) Intercellular adhesion molecule-I gene expression in human endothelial cells. Differential regulation by tumor necrosis factor-a and phorbol myristate acetate. J Biol Chem 267:12030

    Google Scholar 

  46. Wilson T, Treisman R (1988) Removal of poly (A) and consequent degradation of cfos mRNA facilitated by 3′AU-rich sequences. Nature 336:396

    Google Scholar 

  47. Wuthrich RP (1992) Tumor necrosis factor-a-and interleukin1-stimulated intercellular adhesion molecule-1 expression by murine renal tubular epithelial cells is transcriptionally regulated and involves protein kinase C. Renal Physiol Biochem 15:302

    Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Kidney Center, Tokyo Women's Medical College, 8-1 Kawada-cho, 162, Shinjuku-ku, Tokyo, Japan

    K. Tanabe

  2. Department of Urology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, OH, USA

    S. C. Campbell, J. P. Alexander, F. Steinbach, A. C. Novick & E. A. Klein

  3. Department of Pathology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195, Cleveland, OH, USA

    R. R. Tubbs

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  1. K. Tanabe
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Tanabe, K., Campbell, S.C., Alexander, J.P. et al. Molecular regulation of intercellular adhesion molecule 1 (ICAM-1) expression in renal cell carcinoma. Urol. Res. 25, 231–238 (1997). https://doi.org/10.1007/BF00942091

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  • DOI: https://doi.org/10.1007/BF00942091

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