Summary
Intercellular adhesion molecule (ICAM-1) exists as a membrane-associated form (mICAM-1) on the surface of tumour cells as well as a soluble form (sICAM-1). This study analyses the ability of all- trans retinoic acid (RA) to alter both sICAM and mICAM-1 expression in C8161 and Hs294T human melanoma cell lines and investigates the involvement of ICAM-1 in the interaction between tumour and lymphokine-activated killer (LAK) cells using the Cr-51 release assay. Our data showed that 4-day pretreatment of the tumour cells with 10–7 M RA and 10–6 M RA induced an increase in lysis of both cell lines and also increased mICAM-1 expression without having any effect on sICAM-1 levels. Addition of blocking ICAM-1 antibody (10 μg ml–1) to the C8161 cells at an effector:tumour cell ratio of 40:1 caused a 2.3-fold reduction in lysis of tumour cells and a 3-fold reduction in lysis of RA-treated cells. Blocking ICAM-1 antibody at optimum concentrations of 5 μg ml–1 reduced lysis 1.8-fold in control Hs294T cells and 1.3-fold in RA-treated cells. Blocking the HLA–ABC complex had no effect on lysis. The more highly metastatic C8161 cells were found to secrete 4-fold greater levels of sICAM-1 than the poorly metastatic Hs294T cells and addition of sICAM-1 to the assay failed to affect lysis of either cell line but did induce a 2-fold decrease in lysis of RA-treated C8161 cells. Collectively, these data provide further evidence for ICAM-1 involvement in the tumour/LAK cell response and indicates that the RA-induced increase in mICAM-1 levels are partly responsible for the increase in susceptibility of the tumour cells. sICAM-1 appears to be unimportant in evasion of the tumour cells from LAK cell lysis, but may play a role in evasion of RA-treated C8161 cells.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Altomonte, M., Gloghini, A., Bertola, G., Gasparollo, A., Carbone, A., Ferrone, S. & Maio, M. (1993). Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells. Cancer Res 53: 3343–3348.
Aoudjit, F., Bousse, M., Stratowa, C., Voraberger, G. & Audette, M. (1994). Regulation of intercellular adhesion molecule-1 expression by retinoic acid: analysis of the 5′ regulatory region of the gene. Int J Cancer 58: 543–549.
Babina, M., Weber, S. & Henz, B. M. (1997). Retinoic acids and dexamethasone alter cell-surface density of β-2 integrins and ICAM-1 on human leukemic (HMC-1) mast cells. Arch Derm Res 289: 111–115.
Banks, R. E., Gearing, A. J. H., Hemingway, I. K., Norfolk, D. R., Perren, T. J. & Selby, P. J. (1993). Circulating ICAM-1, E-selectin and vascular cell adhesion molecule (VCAM) in human malignancies. Br J Cancer 68: 122–124.
Bassi, V., Vitale, M., Feliciello, A., Deriu, S., Rossi, G. & Fenzi, G. (1995). Retinoic acid induces ICAM-1 hyperexpression in human thyroid carcinoma cell lines. J Clin Endocrinol Metabol 80: 1129–1135.
Becker, J. C., Dummer, R., Schmidt, R. E., Burg, G. & Hartmann, A. A. (1992). Shedding of intercellular adhesion molecule-1 (ICAM-1) from melanoma cell lines – functional consequences on cell-mediated cytotoxicity. Immun Infect 20: 62–63.
Bouillon, M., Tessier, P., Boulianne, R., Destrempe, R. & Audette, M. (1991). Regulation by retinoic acid of ICAM-1 expression on human tumour cell lines. Biochim Biophys Acta 1097: 95–102.
Budnik, A., Grewe, M., Gyufko, K. & Krutmann, J. (1996). Analysis of the production of soluble ICAM-1 molecules by human cells. Exp Hematol 24: 352–359.
Cao, X. T., Chen, G. Y., He, L., Zhang, W. P., Yu, Y. Z. & Wang, J. L. (1997). Involvement of MHC class 1 molecule and ICAM-1 in the enhancement of adhesion and cytotoxic susceptibility to immune effector cells transfected with the interleukin (IL)-2, IL-4 or IL-6 gene. J Cancer Res Clin Oncol 123: 602–608.
Cilenti, L., Toniato, E., Ruggiero, P., Fusco, C., Farina, A. R., Tiberio, A., Hatday, A. C., Gulino, A., Frati, L. & Martinotti, S. (1995). Transcriptional modulation of the human intercellular adhesion molecule gene-1 (ICAM-1) by retinoic acid. Exp Cell Res 218: 263–270.
Creasey, A. A., Smith, H. S., Hackett, A. J., Fukuyama, K., Epstein, W. L. & Madin, S. H. (1979). Biological properties of human melanoma cells in culture. In vitro Cell Dev Biol 15: 342–350.
Eisenthal, A., Marder, O., Maymon, B., Misonzhnik, F., Skornick, Y., Brazowski, E., Czernobilsky, B., Walt, H. & Lifschitz-Mercer, B. (1998). The effect of interferon gamma and tumour necrosis factor alpha on the expression of ICAM-1 and HLA-DR molecules on cells of a human germ cell neoplasm and their susceptibility to lysis by lymphokine-activated killer cells. Pathobiology 66: 205–208.
Gao, Z. & MacKenzie, I. C. (1996). Influence of retinoic acid on the expression of cytokeratins, vimentin and ICAM-1 in human gingival epithelia in-vitro. J Peridont Res 31: 81–89.
Giavazzi, R., Chirivi, R. G. S., Garofalo, A., Rambaldi, A., Hemingway, I., Pigott, R. & Gearing, A. J. H. (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.
Gwin, J. L., Taylor, C. G., Taylor, D. D. & Eisenberg, B. (1996). Role of LFA-3, ICAM-1 and MHC class 1 on the sensitivity of human tumour cells to LAK cells. J Surg Res 60: 129–136.
Harning, R., Mainolfi, E., Bystryn, J. C., Henn, M., Merluzzi, V. J. & Rothlein, R. (1991). Serum levels of circulating ICAM-1 in human malignant melanoma. Cancer Res 51: 5003–5005.
Heymann, D., Godard, A., Raher, S., Ringeard, S., Lassort, D., Blanchard, F. & Harb, J. (1995). Human interleukin for DA cells leukemia inhibitory factor and oncostatin-M enhance membrane expression of intercellular adhesion molecule-1 on melanoma cell but not the shedding of its soluble form. Cytokine 7: 111–117.
Ishiwata, N., Takio, K., Katayama, H., Watanabe, K., Titani, K., Ikeda, Y. & Handa, M. (1994). An alternatively spliced isoform of P-selectin is present in vivo as a soluble molecule. J Biol Chem 269: 23708–23715.
Jackson, A. M., Alexandrov, A. B., Prescott, S., James, K. & Chisholm, G. D. (1992). Role of adhesion molecules in lymphokine-activated killer cell killing of bladder cancer cells: further evidence for a third ligand for leukocyte function associated antigen-1. Immunology 76: 286–291.
Jackson, A. M., Alexandrov, A. B., Gribben, S. C., Esuvarnathan, K. & James, K. (1993). Expression and shedding of ICAM-1 in bladder cancer cells and its role in immunotherapy. Int J Cancer 55: 921–925.
Johnson, J. P., Stade, B. G., Holzmann, B., Schwable, W. & Riethmuller, G. (1989). De novo expression of ICAM-1 in melanoma correlates with increased risk of metastasis. Proc Natl Acad Sci USA 86: 641–644.
Kageshita, T., Yoshii, A., Kimura, T., Kuriya, N., Ono, T., Tsujisaki, M., Imai, K. & Ferrone, S. (1993). Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. Cancer Res 53: 4927–4932.
Kaufman, D. S. (1995). Inhibition of selective signalling events in natural killer cells recognising MHC class 1. Proc Natl Acad Sci (USA) 92: 6484–6488.
Lefor, A. T. & Fabian, D. F. (1998). Enhanced cytolytic activity of tumour infiltrating lymphocytes (TILs) derived from an ICAM-1 transfected tumour in a murine model. J Surg Res 75: 49–53.
Maio, M., Tessitori, G., Pinto, A., Temponi, M., Colombatti, A. & Ferrone, S. (1989). Differential role of distinct determinants of ICAM-1 in immunologic phenomena. J Immunol 143: 181–188.
Marlin, S. D. & Springer, T. A. (1987). Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function associated antigen (LFA-1). Cell 51: 813–819.
Pandolfi, F., Trentin, L., Boyle, L. A., Stamenkovie, I., Byres, H. R., Colvin, R. B. & Kurnick, T. J. (1992). Expression of cell adhesion molecules in human melanoma cell lines and their role in cytotoxicity mediated by tumour infiltrating lymphocytes. Cancer 69: 1165–1173.
Rothlein, R. M., Czajkowski, M. M., O’Neili, S. D., Marlin, E., Mainolfi, E. A. & Merluzzi, V. J. (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: 1665–1669.
Rothlein, R. M., Mainolfi, E. A., Czajkowski, M. & Marlin, S. D. (1991). A form of circulating ICAM-1 in human serum. J Immunol 147: 3788–3793.
Sanchez-Rovira, P., Jimenez, E., Carracedo, J., Barneto, I. C., Ramirez, R. & Aranda, E. (1998). Serum levels of intercellular adhesion molecule 1 (ICAM-1) in patients with colorectal cancer: inhibitory effect on cytotoxicity. Eur J Cancer 34: 394–398.
Smith, M. A., Parkinson, D. R., Cheson, B. D. & Friedman, M. A. (1992). Retinoids in cancer therapy. J Clin Oncol 10: 839–864.
Staunton, D. E., Marlin, S. D., Stratowa, C., Dustin, M. L. & Springer, T. A. (1988). Primary structure of ICAM-1 demonstrates interaction between members of the immunoglobulin and integrin supergene families. Cell 52: 925–933.
Vanky, F., Wang, P., Patarroyo, M. & Klein, E. (1990). Expression of adhesion molecule ICAM-1 and MHC class 1 antigens on human tumour cells is required for their interaction with autologous lymphocytes in vitro. Cancer Immunol Immunother 31: 19–27.
Wang, Z. G., Cao, Y., Durso, C. M. & Ferrone, S. (1992). Differential susceptibility of cultured human melanoma cell lines to enhancement by retinoic acid of intercellular adhesion molecule-1 expression. Cancer Res 52: 4766–4772.
Webb, D. S. A., Mostowski, H. S. & Gerrard, T. L. (1991). Cytokine induced enhancement of ICAM-1 expression results in increased vulnerability of tumour cells to monocyte mediated lysis. J Immunol 146: 3682–3686.
Welch, D. R., Bisi, J. E., Miller, B. E., Conaway, D., Seftor, E. A. & Yohem, K. H. (1991). Characterisation of a highly invasive and spontaneously metastatic human malignant melanoma cell line. Int J Cancer 47: 227–237.
Young, D. G., Jackson, A. M. & James, K. (1997). Purification and characterisation of soluble intercellular adhesion molecule-1 (sICAM-1) and its effect on cell mediated cytolysis of tumour cells. Int J Oncol 10: 827–834.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Alexander, C., Edward, M. & MacKie, R. The role of human melanoma cell ICAM-1 expression on lymphokine activated killer cell-mediated lysis, and the effect of retinoic acid. Br J Cancer 80, 1494–1500 (1999). https://doi.org/10.1038/sj.bjc.6690551
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690551
Keywords
This article is cited by
-
Decitabine facilitates immune recognition of sarcoma cells by upregulating CT antigens, MHC molecules, and ICAM-1
Tumor Biology (2014)
-
Retinoic acid elicits cytostatic, cytotoxic and immunomodulatory effects on uveal melanoma cells
Cancer Immunology, Immunotherapy (2006)