Modulation by retinoic acid (RA) of squamous cell differentiation, cellular RA-binding proteins, and nuclear RA receptors in human head and neck squamous cell carcinoma cell lines (original) (raw)

Abstract

carcinomas in patients with head and neck or lung cancer, and skin cancers in patients with xeroderma pigmentosum (7â€"12). To evaluate the potential application ofretinoids for the prevention and treatment of head and neck premalignancies and SCC,3 we investigated the effects of retinoids on the growth and differentiation of Cultured HNSCC cells (13â€"18). We found that BA inhibited the proliferation of the majority of the HNSCC cell lines we examined and suppressed their transformed phenotype (13, 15, 18). These findings contrasted with previous reports that BA enhanced the growth of normal buccal mucosa cells (19), suggesting a selective inhibition oftumor cells. In addition, BA suppressed squamous differentiation of HNSCC cells (14, 15, 17, 20) and modulated two differentiation pathways in normal laryngeal keratino cytes and papilloma cells (21, 22). The mechanism(s) by which retinoids suppress carcinogenesis and regulate differentiation and the expression of the transformed pheno type in malignant cells has not been elucidated. It is thought that nuclear retinoid receptors, members of the steroid/thyroid hormone! vitamin D receptor family that act as ligand-activated transacting transcription factors, mediate the effects of retinoids on gene expres sion and thereby alter the growth and differentiation of normal and tumor cells. There are two types of retinoid nuclear receptors, RARs and RXRs. Each of the receptor types has at least three subtypes,-a,-@, and-‘y (3, 23â€"26). The RARs bind BA and 9-cis RA, whereas the RXRs bind 9-cis BA but not BA. The RXRs and RARs form het erodimers before binding to specific DNA sequences characterized by direct repeats of (A/G)GCITCA separated by two or five nucleotides, although complex elements have also been identified (24â€"26).Other factors affecting the retinoid-signaling pathway are the CRABP-I and CRABP-II, which have been implicated in controlling the level of BA available for interaction with nuclear receptors by sequestering the retinoid or increasing its catabolism (27, 28). The study presented here was designed to examine the expression of BA-binding proteins and receptors in HNSCC cell lines and their relationship to cell differentiation and responses to BA. MATERIALS AND METHODS Cell CUltUreand BA Treatment Procedures. The fourHNSCCcell lines (Table 1) were grown in monolayer cultures in a 1:1 (v/v) mixture of Dulbec co's modified Eagle's medium and Ham's F12 medium containing 5% FBS at 37°C. BA was dissolved in DMSO at a concentration of 102 Mand was stored in the dark at â€"20°C in N2. Stock solutions were diluted to the appropriate concentration with growth medium. Control cultures received the same amount of DMSO as treated cultures. For growth inhibition studies, cells were grown for 7 days in the absence (control) or presence of 1 @M RA. Medium was 3 The abbreviations used are: SCC, squamous cell carcinoma; HNSCC, head and neck

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References (60)

  1. Lotan,R. Retinoidsandsquamouscell differentiation. In: W. K. Hong and R. Lotan (eds.), Retinoids in Oncology, pp. 43-72. New York: Marcel Dekker, 1993.
  2. Jetten, A. M., Nervi, C., and Vollberg, T. M. Control of squamous differentiation in tracheobronchial and epidermal epithelial cells: role of retinoids. J. NatI. Cancer Inst. Monogr., 13: 93-100, 1992.
  3. DeLuca, L. M. Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J., 5: 2924â€"2933, 1991.
  4. Gudas, L J., Sporn, M. B., and Roberts, A. B. Cellular biology and biochemistry of the retinoids. In: M. B. Sporn, A. B. Roberts, and D. S. Goodman (eds.), The Retinoids, pp. 443â€"520. New York: Raven Press, 1994.
  5. Moon, R. C., and Mehta, R. 0. Retinoid inhibition of experimental carcinogenesis. In: M. I. Dawsonand W. H. Okamura(eds.),Chemistryand Biologyof Synthetic Retinoids, pp. 501â€"518. Boca Raton, FL: CRC Press, 1990.
  6. Shklar, G., Schwartz, J., Grau, D., TrickIer, D. P., and Wallace, K. D. Inhibition of hamster buccal pouch carcinogenesis by 13-cis-retinoic acid. Oral Surg., 50: 45â€"52, 1980.
  7. Hong, W. K., Endicott, J., Itt!, L M., Dons, W., Batsakis, J. 0., Bell, R., Fofonoff, S., Byers,R.,Atkinson, E. N.,Vaughan, C.,Toth,B. B., Kramer, &, Dimery, I. W., Skipper, P., and Strong, S. !3-cis Retinoic acid in the treatment of oral leukoplakia. N. EngI. J. Med., 315: 1501â€"1505, 1986.
  8. Chiess, F., Tradati, N., Marazza, M., Rossi, N., Boracchi, P., Mariani, L, Clerici, M., Formelli, F., Barzan, L, Carrassi, A., Pastorini, A., Cameriini, T., Giardini, R., Zurrida, S.,Minn,F. L.,Costa,A.,DcPalo,G.,andVeronesi, U. Prevention of local relapses and new localisations of oral leukoplakia with the synthetic retinoid fen retinide (4-HPR). Preliminary results. Oral Oncot. Eur. i. Cancer, 28B: 97â€"102, 1992.
  9. Hong, W. K., Lippman, S. M., Itri, L M., Karp, D. D., Lee, J. S., Byers, R. M., Schantz, S. S., Kramer, A. M., Lotan, R., Peters, L L, Dimery, I. W., Brown, B. W., and Goepfert, H. Prevention of second primary tumors with isotretinoin in squamous cell carcinoma of the head and neck. N. Engl. J. Med., 323: 795â€"80!, 1990.
  10. Pastorino, U., Infante, M., Maioli, M., Chiesa, G., Buyse, M., Pirket, P., Rosementz, N., Clerici, M., Soresi, E., Valente, M., Belloni, P. A., and Ravasi, G. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J. Clin. Oncol., 11: 1216â€"1222,1993.
  11. Kraemer, K. H., DiGiovanna, J. J., Moshell, A. N., Tarone, R. E., and Peck, G. L Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N. EngI. J. Med., 318: 1633â€"1637, 1988.
  12. Smith, M. A., Parkinson, D. R., Cheson, B. D., and Friedman, M. A. Retinoids in cancer therapy. J. Clin. Oncol., 10: 839â€"864, 1992.
  13. Lotan, R., Lotan, D., Sacks, P. 0., and Hong, W. K. Distinct effects of retinoic acid on the in vitro growth and cell surface glycoconjugates of two human head and neck squamous cell carcinomas. Int. J. Cancer, 40: 224â€"229, 1987.
  14. Sacks, P. G., Oke, V., Amos, B., Vasey, T., and Lotan, R. Modulation of growth, differentiation, and glycoprotein synthesis by @3-all-trans retinoic acid in a multicel lular tumorspheroidmodel for squamouscarcinomaof the head and neck. tnt. J. Cancer, 45: 926â€"933, 1989.
  15. Jeuen, A. M., Kim, J. S., Sacks, P. G., Rearick, J. I., Lotan, D., Hong, W. K., and Lotan, R. Suppression of growth and squamous cell differentiation markers in cultured human head and neck squamous carcinoma cells by a-all trans retinoic acid. Int. J. Cancer, 45: 195â€"202, 1990.
  16. Lotan,R., Lotan,D., and Sacks, P. 0. Inhibitionof tumorcell growthby retinoids. MethodsEnzymol., 190: 100â€"110, 1990.
  17. Poddar, S., Hong, K., Thacher, S., and Lotan, R. Suppression of type I transglutami nase, involucrin and keratin K! in cultured human head and neck squamous carci noma 1483 cells by retinoic acid. lot. J. Cancer, 48: 239â€"247, 1991.
  18. Kim, J. S., Steck, P. A., Gallick, G. E., Lee, J. S., Blick, M., Hong, W. K., and Lotan, R. Suppressionby retinoicacid of epidermalgrowthfactorreceptorautophosphory lation and glycosylation in cultured human head and neck squamous carcinoma cells. J. Nail. CancerInst. Monogr.,13: 101â€"110, 1992.
  19. Sundqvist, K., Liu, Y., Arvidson, K., Ormstad, K., Nilsson, L, Toftgard, R., and Grafstrom, R. C. Growth regulation of serum-free cultures of epitheial cells from normal human buccal mucosa. In Vitro Cell Dev. Biol., 27: 562â€"568, 1991.
  20. Reiss, M., Pitman, S. W., and Sartorelli, A. C. Modulation of the terminal differen tiation of human squamous carcinoma cells in vitro by all-trans-retinoic acid. J. NaIl. Cancer Inst., 74: 1015-1023, 1985.
  21. Mendelsohn, M. 0., DiLorenzo, T. P., Abramson, A. L, and Steinberg, B. M. Retinoic acid regulates, in vitro, the two normal pathways of differentiation of human laryngealkeratinocytes.In Vitro Cell Dev. Biol., 27A: 137â€"141, 1991.
  22. Chirgwin, J. M., Pryzbyla, A. E., MacDonald, R. J., and Rutter, W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochem istry, 18: 5294â€"5299, 1979.
  23. Feinberg, A. P., and Vogelstein, B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem., 132: 6â€"13, 1983.
  24. Xu, X-C., Clifford, J. L, Hong, W. K., and Lotan, R. Detection of nuclear retinoic acid receptor mRNAs in histological tissue sections using non-radioactive in situ hybridization histochemistry. Diagn. Mol. Pathol., 3: 122â€"131,1994.
  25. Gaub, M. P., Lutz, Y., Ruberte, E., Petkovich, M., Brand, N., and Chambon, P. Antibodies specific to the retinoic acid human nuclear receptors a and @. Proc. NaIl. Acad. Sd. USA, 86: 3089-3093, 1989.
  26. Rochette-Egly, C., Lutz, Y., Saunders, M., Scheuer, I., Gaub, M-P., and Chambon, P. Retinoic acid receptor y@specific immunodetection and phosphorylation. J. Cell Biol., 115: 535â€"545, 1991.
  27. Fuchs, E., and Green, H. Regulation of terminal differentiation of cultured human keratinocytes by vitamin A. Cell, 25: 617â€"625, 1981.
  28. Mohla, S., and Gause, B. In vivo growth inhibition of human pharyngeal squamous cell carcinoma cell line (FADU) by retinoids. Proc. Am. Assoc. Cancer Res., 30: A306, 1989.
  29. Ong, D. E., Newcomer, M. E., and Chytil, F. Cellular retinoid-binding proteins. In: M.B. Sports, A. B. Roberts, andD. S. Goodman(eds.),TheRetinoids, pp.283â€"317. New York: Raven Press, 1994.
  30. Fuchs, E. Epidermal differentiation: the bare essentials. J. Cell Biol., 111: 2807â€"2814, 1990.
  31. Masui, T., Wakefield, L M., Lechner, J. F., LaVeck, M. A., Sporn, M. B, and Harris, C. C. Type-a transforminggrowth factor is the primarydifferentiation-inducing serumfactorfornormalhumanbronchial epithelial cells.Proc.NatI.Acad.Sci.USA, 83: 2438â€"2442,1986.
  32. Astrom, A., Tavakkol, A., Petterson, U., Cromie, M., Elder, J. T., and Voorhees, J. J. Molecular cloning of two human cellular retinoic acid-binding proteins (CRABP). Retinoic acid-induced expression of CBABP-II but not CBABP-I in adult human skin in vivo and in skin fibroblasts in vitro. J. Biol. Chem., 266: 17662â€"17666,1991.
  33. Siegenthaler, G., Saurat, J. H., and Ponec, M. Terminal differentiation in cultured human keratinocytes is associated with increased levels of cellular retinoic acid binding protein. Exp. Cell Res., 178: 114â€"126,1988.
  34. Siegenthaler, G., Samson, J., Bernard, J. P., Fiore-Donno, G., and Saurat, J. H. Retinoid-binding proteins in human oral mucosa. J. Oral Pathol., 17: 106â€"112, 1988.
  35. Ong, D. E., Goodwin, W. J., Jesse, R. H., and Griffm, A. C. Presence of cellular retinol and retinoic acid-binding proteins in epidermoid carcinoma of the oral cavity and oropharynx. Cancer (Phila.), 49: 1409â€"1412,1982.
  36. Rallet, A., and Jardillier, J. C. Cellular binding proteins for retinol and retinoic acid in head and neck carcinomas and in human breast cancer cell lines. Steroids, 52: 397â€"398,1988.
  37. Sanquer, S., Eller, M. S., and Gilchrest, B. A. Retinoids and state of differentiation modulate CRABP II gene expression in a skin equivalent. J. Invest. Dermatol., 100: 148â€"153, 1993.
  38. Durand, B., Saunders, M., Leroy, P., Leid, M., and Chambon, P. All-trans and 9-cis retinoic acid induction of CBABPII transcription is mediated by RAR-RXR bet erodimersboundto DR1andDR2repeatedmotifs.Cell,71: 73â€"85, 1992.
  39. Crowe, D. L, Hu, L., Gudas, L. J., and Rheinwald, J. G. Variable expression of retinoic acid receptor (BAR-beta) mRNA in human oral and epidermal keratinocytes: relation to keratin 19 expression and keratinization potential. Differentiation, 48: 199â€"208, 1991.
  40. Hu, L, Crowe, D. L, Rheinwald, J. G., Chambon, P., and Gudas, L i. Abnormal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines. Cancer Res., 51: 3972â€"3981, 1991.
  41. Xu, X-C., Ro, J. Y., Lee, J. S., Shin, D. M., Hong, W. K., and Lotan, R. Differential expression of nuclear retinoid receptors in normal, premalignant, and malignant head and neck tissues. Cancer Res., 54: 3580â€"3587, 1994.
  42. Reppucci, A. D., DiLorenzo, T. P., Abramson, A. L., and Steinberg, B. M. In vitro modulation of human laryngeal papilloma cell differentiation by retinoic acid. Otolaryngol. Head Neck Surg., 105: 528â€"532, 1991.
  43. Lotan, R., and Clifford, J. L. Nuclear receptors for retinoids: mediators of retinoid effects on normal and malignant cells. Biomed. Pharmacother., 45: 145â€"156, 1990.
  44. Leroy, P., Krust, A., Kastner, P., Mendelsohn, C., Zelent, A., and Chambon, P. Retinoicacidreceptors. In: 0. Morriss-Kay (ed), Retinoidsin NormalDevelopment and Teratogenesis, pp. 7â€"25. New York: Oxford University Press, 1992.
  45. Pfahl, M., Zhang, X-K., Lehmann, J. M., Husmann, M., Graupner, G., and Hoffmann, B. Molecularmechanismsof retinoicacid action.In: 0. Morriss-Kay(ed), Retinoids in Normal Development and Teratogenesis, pp. 51â€"64. New York: Oxford University Press, 1992.
  46. Mangelsdorf, D. Umesono, K., and Evans, R. M. The retinoid receptors. In: M. B. Sporn, A. B. Roberts, and D. S. Goodman (eds.), The Retinoids, pp. 319â€"349. New York: Raven Press, 1994.
  47. Boylan, J. F., and Gudas, J. L Overexpression of the cellular retinoic acid binding protein-I (CRABP-I) results in reduction in differentiation-specific gene expression in F9 teratocarcinoma cells. J. Cell Biol., 112: 965â€"979,1991.
  48. Boylan, J. F., and Gudas, J. L. The level of CBABP-I expression influences the amounts and types of all-trans-retinoic acid metabolites in P9 teratocarcinoma cells. J. Biol.Chem.,267:21486â€"21491, 1992.
  49. Sacks, P. 0., Parnes, S. M., Gallick, G. E., Mansouri, Z., Lichtner, R., Satya-Prakash, K. L., Pathak,S. and Parsons,D. F. Establishmentand characterization of two new squamous cell carcinoma cell lines derived from tumors of the head and neck. Cancer Res., 48: 2858â€"2866, 1988.
  50. Gown, A. M., and Vogel, A. M. Monoclonal antibodies to human intermediate filament proteins. II. Distribution of ifiament proteins in normal human tissues. Am. J.Pathol., 114:309â€"321, 1985.
  51. Floyd, E. B., and Jetten, A. M. Regulation of type I (epidermal) transglutaminase mRNA levels during squamous differentiation: down regulation by retinoids. Mol. Cell Biol., 9: 4846â€"4851, 1989.
  52. Eckert, R. L., and Green, H. Structure and evolution of the human involucrin gene. Cell, 46: 583â€"589, 1986.
  53. Steiner, P. M., Parry, D. A. D., Idler, W. W., Johnson, L. D., Steven, A. C., and Roop, D. R. Amino acid sequences of mouse and humanepidermaltype II keratinsof M@ 67,000 provide a systematic basis for the structural and functional diversity of the end domains of keratin intermediate filament subunits. J. Biol. Chem., 260: 7142â€"7149, 1985.
  54. Petkovich, M., Brand, N. J., Krust, A., and Chambon, P. A human retinoic acid receptor which belongs to the family of nuclear receptors. Nature (Land.), 330: 444â€"450, 1987.
  55. Brand, N., Petkovitch, M., Krust, A., Chambon, P., de The, H., Marchio, A., Tiollas, P., and Dejean, A. Identificationof a second humanretinoic acid receptor.Nature (Land.), 332: 850â€"853, 1988.
  56. Krust,A., Kastner,P., Petkovich, M., Zelent, A., and Chambon,P. A thirdhuman retinoic acid receptor, hBAR-y. Proc. Natl. Acad. Sci. USA, 86: 5310â€"5314, 1989.
  57. Manglesdorf, D. J., Borgmeyer, U., Heyman, R. A., Zhao, J. Y., Ong, E. S., Oro, A. E., Kakizuka, A., and Evans, R. M. Characterization of three RXR genes that mediate the action of 9-cis retinoic acid. Genes Dev., 6: 329â€"344, 1992.
  58. Giguere, V., Lyn, S., Yip, P., Siu, C. H., and Amin, S. Molecular cloning of cDNA encoding a second cellular retinoic acid-binding protein. Proc. NatI. Acad. Sci. USA, 87: 6233â€"6237, 1990.
  59. MacGregor, T. M., Copeland, N. G., Jenkins, N. A., and Giguere, V. The murine gene for cellular retinoic acid-binding protein type II. J. Biol. Chem., 267: 7777â€"7783, 1992.
  60. Dugaiczyk, A., Haron, J. A., Stone, E. M., Dennison, 0. E., Rothblum, K. N., and Swartz, R. J. Cloning and sequencing of a deoxyribonucleic acid copy of glyceral dehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle. Biochemistry, 22: 1605-1613, 1983.