Abstract
Serum soluble interleukin-2 receptor (sIL-2R), intercellular adhesion molecule-1 (sICAM-1) and interleukin-10 (IL-10) have each been reported as useful markers for melanoma progression. To evaluate the clinical relevance of these three markers, we simultaneously analysed their serum levels in patients with melanoma. A longitudinal study with a 3-year follow-up was performed and different stages of the disease were considered. Mean values of sIL-2R were significantly higher than in normal controls in all stages and correlated with the disease progression. The prognosis of patients with levels > 529 U/ml of sIL-2R was significantly poorer than in patients with sIL-2R levels < 529 U/ml. Levels of sICAM-1 were also elevated in melanoma patients, specially at the time of the metastatic disease. Serum IL-10 levels were more frequently detectable in the patients that developed metastasis during follow-up, and the prognosis of patients with detectable IL-10 levels was significantly poorer than in those patients with IL-10 undetected levels. Statistical analysis based on Logistic and Cox regression models showed that only sex, stage and sIL-2R value are factors significantly associated with metastatic progression. Moreover, high levels of sIL-2R could be a risk factor for malignant progression in melanoma. © 2000 Cancer Research Campaign
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References
Alileche A, Plaisance S, Han DS, Rubinstein E, Mingari C, Bellomo R, Jasmin C and Azzarone B (1993) Human melanoma cell line M14 secretes a functional interleukin 2. Oncogene 8: 1791–1796
Altamonte M, Colizzi F, Esposito G and Maio M (1991) Circulating intercellular adhesion molecule-1 as a marker of disease progression in cutaneous melanoma. N Engl J Med 327: 959–962
Banks RE, Gearing AJH, Hemingway IK, Norfolk DR, Perren TJ and Selby PJ (1993) Circulating intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell-adhesion molecule-1 (VCAM-1) in human malignancies. Br Cancer Res 68: 122–124
Becker JC, Dummer R, Hartmann AA, Burg G and Schmidt RE (1991) Shedding of ICAM-1 from human melanoma cell lines induced by IFN-γ and tumour necrosis factor-α. J Immunol 147: 4398–4401
Boyano MD, García-Vázquez MD, Gardeazabal J, García de Galdeano A, Smith-Zubiaga I, Cañavate ML, Ratón JA, Bilbao I and Díaz-Pérez JL (1997) Serum-soluble IL-2 receptor and IL-6 levels in patients with melanoma. Oncology 54: 400–406
Burton J, Goldman CK, Rao P, Moos M and Waldmann TA (1990) Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin-2 receptor. Proc Natl Acad Sci USA 78: 7329–7333
Chen Q, Daniel V, Maher DW and Hersey P (1994) Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma. Int J Cancer 56: 755–760
Dummer W, Becker JC, Achwaaf A, Leverkus M, Moll T and Brocker EB (1995) Elevated serum levels of interleukin-10 in patients with metastatic malignant melanoma. Melanoma Res 5: 67–68
Fernandez-Botran R (1991) Soluble cytokine receptors: their role in immuneregulation. FASEB J 5: 2567–2574
Fierro MT, Lisa F, Novelli M, Beretero M and Bernengo MG (1992) Soluble Interleukin-2 receptor, CD4 and CD8 levels in melanoma: A longitudinal study. Dermatology 184: 182–189
Fiorentino DF, Zlotnik A, Mosmann TR, Howard M and O'Garra A (1991a) IL-10 inhibits cytokine production by activated macrophages. J Immunol 147: 3815–3822
Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW and O'Garra A (1991b) IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol 146: 3444–3451
García de Galdeano A, Boyano MD, Smith-Zubiaga I and Cañavate ML (1996) B16F10 murine melanoma cells express interleukin-2 and a functional interleukin-2 receptor. Tumor Biol 17: 155–167
Giavazzi R, Chirivi RGS, Garafalo A, Rambaldi A, Hemingway I and Pigott R (1992) Soluble intercellular adhesion molecule-1 is released by human melanoma cells and is associated with tumour growth in nude mice. Cancer Res 52: 2628–2630
Harning R, Mainolfi E, Bystryn JC, Henn M, Merluzzi VJ and Rothlein R (1990) Serum levels of circulating intercellular adhesion molecule-1 in human malignant melanoma. Cancer Res 51: 5003–5005
Howard M, O'Garra A, Ishida H, de Waal MR and de Vries J (1992) Biological properties of Interleukin-2. J Clin Immunol 12: 239–247
Huang S, Xie K, Bucana CD, Ullrich SE and Bar-Eli M (1996) Interleukin 10 suppresses tumour growth and metastasis of human melanoma cells: potential inhibition of angiogenesis. Clin Cancer Res 2: 1969–1979
Johnson JP, Stade BG, Holtzmann B, Schwable W and Riethmuller G (1989) De novo expression of intercellular adhesion molecule 1 in melanomas correlates with increased risk of metastasis. Proc Natl Acad Sci USA 86: 641–644
Josimovic-Alasevic O, Herrmann T and Diamantstein T (1988) Demonstrations of two distinct forms of released low-affinity type interleukin-2 receptors. Eur J Immunol 18: 1855–1857
Kageshita T, Yoshii A, Kimura N, Ono t, Tsujisaki M, Imai K and Ferrone S (1993) Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. Cancer Res 53: 4927–4932
Kerbel RS (1992) Expression of multi-cytokine resistance and multigrowth factor independence in advanced stage metastatic cancer. Am J Pathol 141: 519–524
Landáyi A, Nagy JO, Jeney A and Tímar J (1998) Cytokine sensitivity of metastatic human melanoma cells lines- simultaneous inhibition of proliferation and enhancement of gelatinase activity. Pathology Oncology Res 2: 108–114
Marlin SD and Springer TA (1987) Intecellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 (LFA-1). Cell 15: 831–843
Natali P, Nicotra MR, Cavalieri R, Bigotti A, Romano G, Temponi M and Ferrone S (1990) Differential expression of intercellulat adhesion molecule 1 in primary and metastatic melanoma lesions. Cancer 50: 1271–1278
Plaisance S, Rubinstein E, Alileche A, Han DS, Sahraoui Y, Mingari C, Bellomo R, Rimoldi D, Colombo MP and Jasmin C (1993) Human melanoma cells express a functional interleukin-2 receptor. Int J Cancer 55: 164–170
Rubin LA and Nelson DL (1990) The soluble interleukin-2 receptor: Biology, function and clinical application. Ann Inter Med 113: 619–627
Sato T, McCue P, Masuoka K, Salwen S, Lattime EC, Mastrangelo MJ and Berd D (1916) Interleukin 10 production by human melanoma. Clin Cancer Res 2: 1383–1390
Schadendorf D, Diehl S, Zuberbier T, Schadendorf C and Henz BM (1996) Quantitative detection of soluble adhesion molecules in sera of melanoma patients correlates with clinical stage. Dermatology 192: 89–93
Staunton DE, Daustin ML, Erickson HP and Springer TA (1990) The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1. Cell 61: 243–254
Taga K and Tosako G (1992) IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 148: 1143–1147
Timonen T, Patarroyo M and Gahmberg CG (1988) CD11a-c/CD18 and GP84 (LB-2) adhesion molecules on human large granular lymphocytes and their participation in natural killing. J Immunol 141: 1041–1046
Tsujisaki M, Imai K, Hirata H, Hanzawa Y, Masuya J, Nakano T, Sugiyama T, Matsui M, Hinoda Y and Yachi A (1991) Detection of circulating intercellular adhesion molecule-1 antigen in malignant diseases. Clin Exp Immunol 85: 3–8
Vanky F, Wang P, Patarroyo M and Klein E (1990) Expression of the adhesion molecule ICAM-1 and major histocompatibility complex class I antigens on human tumour cells is required for their interaction with autologous lymphocytes in vitro. Cancer Immunol Immunother 31: 19–27
Yue FY, Dummer R, Geertsen R, Hofbauer G, Laine E, Manolio S and Burg G (1997) Interleukin-10 is a growth factor for human melanoma cells and down-regulates HLA class-I, HLA class-II and ICAM-1 molecules. Int J Cancer 71: 630–637
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Boyano, M., Garcia-Vázquez, M., López-Michelena, T. et al. Soluble interleukin-2 receptor, intercellular adhesion molecule-1 and interleukin-10 serum levels in patients with melanoma. Br J Cancer 83, 847–852 (2000). https://doi.org/10.1054/bjoc.2000.1402
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DOI: https://doi.org/10.1054/bjoc.2000.1402
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