Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Transfer of Interleukin 2 Receptor Genes Into Squamous Cell Carcinoma: Modification of Tumor Cell Growth

Transfer of Interleukin 2 Receptor Genes Into Squamous Cell Carcinoma: Modification of Tumor Cell... Abstract Objective: Human squamous cell carcinomas of the head and neck (SCCHN) have been shown to express interleukin 2 receptor (IL-2R), and binding of the ligand, IL-2, to the receptor results in tumor growth inhibition in vitro or in vivo in an SCCHN xenograft model in nude mice. To optimize growth inhibitory effects of IL-2, expression of the α or γ chains of IL-2R in SCCHN was experimentally modified by transfection of tumor cells with the respective IL-2R genes or the lacZ gene as control. Design: Using plasmid vectors containing the IL-2Rα chain gene under the control of a cytomegalovirus promoter or the IL-2Rγ chain gene under the control of a Rous sarcoma virus promoter, the IL-2R genes were transferred by lipofection into SCCHN cell lines. Stable transfectants were selected, cloned by limiting dilution, and clones were compared with the parental cell lines for their sensitivity to the growth-inhibitory effect of IL-2. Results: Transfer of the IL-2Rα chain gene into SCCHN cells resulted in significant upregulation of expression of the IL-2Rα chain on tumor cell surface but not in increased tumor growth inhibition by IL-2. In contrast, SCCHN IL-2Rγ transfectants, which expressed IL-2Rγ chain transcripts as confirmed in RNase protection assays, were significantly inhibited in growth and were sensitive to lower concentrations of IL-2 than the parental cell lines. Conclusions: Genetic modification of IL-2R expression on IL-2R—positive tumor cells in culture significantly alters their proliferative response to IL-2. These observations open a way for developing new strategies for therapy of SCCHN based on direct interactions of IL-2 with its receptor on tumor cells.(Arch Otolaryngol Head Neck Surg. 1993;119:1229-1235) References 1. Taniguchi T, Minami Y. The IL-2/IL-2 receptor system . Cell . 1993;73:5-8.Crossref 2. Takeshita T, Asao H, Ohtani K, et al. Cloning of the gamma chain of the human IL-2 receptor . Science . 1992;257:379-382.Crossref 3. Plaisance S, Rubinstein E, Alileche A, et al. Expression of the interleukin-2 receptor on human fibroblasts and its biological significance . Int Immunol . 1992;4:739-746.Crossref 4. Weidmann E, Sacchi M, Plaisance S, et al. Receptors for interleukin-2 on human squamous cell carcinoma cell lines and tumor in situ . Cancer Res . 1992;52:5963-5970. 5. Arzt E, Steizer G, Renner U, Lange M, Muller OA, Stalla GK. Interleukin-2and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures . J Clin Invest . 1992;90:1944-1951.Crossref 6. Rimoldi D, Salvi S, Hartmann F, et al. Expression of IL-2 receptors in human melanoma cells . Anticancer Res . 1993;13:555-564. 7. Lin WC, Yasumura S, Weidmann E, et al. Growth inhibition by IL-2 of human epithelial tumor cell lines transduced with the IL-2 receptor genes . AACR Proc . 1993; 34:58. 8. Rabinowich H, Vitolo D, Altarac S, Herberman, RB, Whiteside TL. Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2–activated natural killer cells . J Immunol . 1992;149:340-349. 9. Whiteside TL, Letessier E, Hirabayashi H, et al. Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin-2 in patients with advanced squamous cell carcinoma of the head and neck. Cancer Res. In press. 10. Forni G, Cavallo GP, Giovarelli M, et al. Tumor immunotherapy by local injection of interleukin-2 and non-reactive lymphocytes . Prog Exp Tumor Res . 1988;32:187-212. 11. Cortesina G, DeStefani A, Giovarelli M, et al. Treatment of recurrent squamous cell carcinoma of head and neck with low dose of interleukin-2 (IL-2) injected perilymphatically . Cancer . 1988;62:2482-2487.Crossref 12. Heo DS, Snyderman C, Gollin SM, et al. Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines . Cancer Res . 1989;49:5167-5175. 13. Yasumura S, Hirabayashi H, Schwartz DR, et al. Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck . Cancer Res . 1993;53:1461-1468. 14. Sacchi M, Snyderman CH, Heo DS, et al. Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine activated killer cells and interleukin-2 . Cancer Res . 1990;50:3113-3118. 15. Heo DS, Park JG, Hata K, et al. Evaluation of tetrazolium-based semi-automatic colorimetric assay for measurement of antitumor cytotoxicity . Cancer Res . 1990; 50:3681-3690. 16. Freimark BD, Robb RJ. Functional expression of native and chimeric human and murine IL-2 receptor chains in an IL3-dependent murine cell line . Lymphokine Res . 1990;9:507-514. 17. Lin WC, Pretlow TP, Pretlow TG, Culp LA. Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression . Cancer Res . 1990;50:2808-2817. 18. Freshney RI. Culture of Animal Cells . 2nd ed. New York, NY: Wiley-Liss Inc, 1987. 19. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction . Anal Biochem . 1987;162:156-159.Crossref 20. Arima N, Kamio M, Imada K, et al. Pseudo-high affinity interleukin-2 (IL-2) receptors lacks the third component that is essential for functional IL2 binding and signalling . J Exp Med . 1992;176:1265-1272.Crossref 21. Gansbacher B, Zier K, Daniels B, et al. Interleukin-2 gene transfer into tumor cells abbrogates tumorigenicity and induces protected immunity . J Exp Med . 1990;172: 1217-1224.Crossref 22. Golumbek P, Lazenby A, Levitsky H, et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4 . Science . 1991;254:713-716.Crossref 23. Porgador A, Bannerji R, Wantanabe Y, et al. Antimetastatic vaccination of tumorbearing mice with two types of IFN-gamma gene inserted tumor cells . J Immunol . 1993;150:1458-1470. 24. Sacchi M, Klapan I, Johnson, JT, Whiteside TL. Antiproliferative effects of cytokines on squamous cell carcinoma . Arch Otolaryngol Head Neck Surg . 1991;117:321-326.Crossref 25. Orosz P, Echtenacher B, Falk W, et al. Enhancement of experimental metastasis by tumor necrosis factor . J Exp Med . 1993;177:1391-1398.Crossref 26. Rosenberg SA, Lotze MT, Yang JC, etal. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients . Ann Surg . 1989;210:474-485.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Otolaryngology - Head & Neck Surgery American Medical Association

Transfer of Interleukin 2 Receptor Genes Into Squamous Cell Carcinoma: Modification of Tumor Cell Growth

Loading next page...
 
/lp/american-medical-association/transfer-of-interleukin-2-receptor-genes-into-squamous-cell-carcinoma-KcKVJfBHZo

References (28)

Publisher
American Medical Association
Copyright
Copyright © 1993 American Medical Association. All Rights Reserved.
ISSN
0886-4470
eISSN
1538-361X
DOI
10.1001/archotol.1993.01880230075012
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: Human squamous cell carcinomas of the head and neck (SCCHN) have been shown to express interleukin 2 receptor (IL-2R), and binding of the ligand, IL-2, to the receptor results in tumor growth inhibition in vitro or in vivo in an SCCHN xenograft model in nude mice. To optimize growth inhibitory effects of IL-2, expression of the α or γ chains of IL-2R in SCCHN was experimentally modified by transfection of tumor cells with the respective IL-2R genes or the lacZ gene as control. Design: Using plasmid vectors containing the IL-2Rα chain gene under the control of a cytomegalovirus promoter or the IL-2Rγ chain gene under the control of a Rous sarcoma virus promoter, the IL-2R genes were transferred by lipofection into SCCHN cell lines. Stable transfectants were selected, cloned by limiting dilution, and clones were compared with the parental cell lines for their sensitivity to the growth-inhibitory effect of IL-2. Results: Transfer of the IL-2Rα chain gene into SCCHN cells resulted in significant upregulation of expression of the IL-2Rα chain on tumor cell surface but not in increased tumor growth inhibition by IL-2. In contrast, SCCHN IL-2Rγ transfectants, which expressed IL-2Rγ chain transcripts as confirmed in RNase protection assays, were significantly inhibited in growth and were sensitive to lower concentrations of IL-2 than the parental cell lines. Conclusions: Genetic modification of IL-2R expression on IL-2R—positive tumor cells in culture significantly alters their proliferative response to IL-2. These observations open a way for developing new strategies for therapy of SCCHN based on direct interactions of IL-2 with its receptor on tumor cells.(Arch Otolaryngol Head Neck Surg. 1993;119:1229-1235) References 1. Taniguchi T, Minami Y. The IL-2/IL-2 receptor system . Cell . 1993;73:5-8.Crossref 2. Takeshita T, Asao H, Ohtani K, et al. Cloning of the gamma chain of the human IL-2 receptor . Science . 1992;257:379-382.Crossref 3. Plaisance S, Rubinstein E, Alileche A, et al. Expression of the interleukin-2 receptor on human fibroblasts and its biological significance . Int Immunol . 1992;4:739-746.Crossref 4. Weidmann E, Sacchi M, Plaisance S, et al. Receptors for interleukin-2 on human squamous cell carcinoma cell lines and tumor in situ . Cancer Res . 1992;52:5963-5970. 5. Arzt E, Steizer G, Renner U, Lange M, Muller OA, Stalla GK. Interleukin-2and interleukin-2 receptor expression in human corticotrophic adenoma and murine pituitary cell cultures . J Clin Invest . 1992;90:1944-1951.Crossref 6. Rimoldi D, Salvi S, Hartmann F, et al. Expression of IL-2 receptors in human melanoma cells . Anticancer Res . 1993;13:555-564. 7. Lin WC, Yasumura S, Weidmann E, et al. Growth inhibition by IL-2 of human epithelial tumor cell lines transduced with the IL-2 receptor genes . AACR Proc . 1993; 34:58. 8. Rabinowich H, Vitolo D, Altarac S, Herberman, RB, Whiteside TL. Role of cytokines in the adoptive immunotherapy of an experimental model of human head and neck cancer by human IL-2–activated natural killer cells . J Immunol . 1992;149:340-349. 9. Whiteside TL, Letessier E, Hirabayashi H, et al. Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin-2 in patients with advanced squamous cell carcinoma of the head and neck. Cancer Res. In press. 10. Forni G, Cavallo GP, Giovarelli M, et al. Tumor immunotherapy by local injection of interleukin-2 and non-reactive lymphocytes . Prog Exp Tumor Res . 1988;32:187-212. 11. Cortesina G, DeStefani A, Giovarelli M, et al. Treatment of recurrent squamous cell carcinoma of head and neck with low dose of interleukin-2 (IL-2) injected perilymphatically . Cancer . 1988;62:2482-2487.Crossref 12. Heo DS, Snyderman C, Gollin SM, et al. Biology, cytogenetics, and sensitivity to immunological effector cells of new head and neck squamous cell carcinoma lines . Cancer Res . 1989;49:5167-5175. 13. Yasumura S, Hirabayashi H, Schwartz DR, et al. Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck . Cancer Res . 1993;53:1461-1468. 14. Sacchi M, Snyderman CH, Heo DS, et al. Local adoptive immunotherapy of human head and neck cancer xenografts in nude mice with lymphokine activated killer cells and interleukin-2 . Cancer Res . 1990;50:3113-3118. 15. Heo DS, Park JG, Hata K, et al. Evaluation of tetrazolium-based semi-automatic colorimetric assay for measurement of antitumor cytotoxicity . Cancer Res . 1990; 50:3681-3690. 16. Freimark BD, Robb RJ. Functional expression of native and chimeric human and murine IL-2 receptor chains in an IL3-dependent murine cell line . Lymphokine Res . 1990;9:507-514. 17. Lin WC, Pretlow TP, Pretlow TG, Culp LA. Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression . Cancer Res . 1990;50:2808-2817. 18. Freshney RI. Culture of Animal Cells . 2nd ed. New York, NY: Wiley-Liss Inc, 1987. 19. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction . Anal Biochem . 1987;162:156-159.Crossref 20. Arima N, Kamio M, Imada K, et al. Pseudo-high affinity interleukin-2 (IL-2) receptors lacks the third component that is essential for functional IL2 binding and signalling . J Exp Med . 1992;176:1265-1272.Crossref 21. Gansbacher B, Zier K, Daniels B, et al. Interleukin-2 gene transfer into tumor cells abbrogates tumorigenicity and induces protected immunity . J Exp Med . 1990;172: 1217-1224.Crossref 22. Golumbek P, Lazenby A, Levitsky H, et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4 . Science . 1991;254:713-716.Crossref 23. Porgador A, Bannerji R, Wantanabe Y, et al. Antimetastatic vaccination of tumorbearing mice with two types of IFN-gamma gene inserted tumor cells . J Immunol . 1993;150:1458-1470. 24. Sacchi M, Klapan I, Johnson, JT, Whiteside TL. Antiproliferative effects of cytokines on squamous cell carcinoma . Arch Otolaryngol Head Neck Surg . 1991;117:321-326.Crossref 25. Orosz P, Echtenacher B, Falk W, et al. Enhancement of experimental metastasis by tumor necrosis factor . J Exp Med . 1993;177:1391-1398.Crossref 26. Rosenberg SA, Lotze MT, Yang JC, etal. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients . Ann Surg . 1989;210:474-485.Crossref

Journal

Archives of Otolaryngology - Head & Neck SurgeryAmerican Medical Association

Published: Nov 1, 1993

There are no references for this article.