Establishment of a Langerhans cell histiocytosis lesion cell line with dermal dendritic cell characteristics

Murakami,Ichiro; Gogusev,Jean; Jaubert,Francis; Matsushita,Michiko; Hayashi,Kazuhiko; Miura,Ikuo; Tanaka,Takehiro; Oka,Takashi; Yoshino,Tadashi

doi:10.3892/or.2014.3567

Establishment of a Langerhans cell histiocytosis lesion cell line with dermal dendritic cell characteristics

Authors:
- Ichiro Murakami
- Jean Gogusev
- Francis Jaubert
- Michiko Matsushita
- Kazuhiko Hayashi
- Ikuo Miura
- Takehiro Tanaka
- Takashi Oka
- Tadashi Yoshino
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Affiliations: Division of Molecular Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8503, Japan, Inserm U507 and U1016, Institut Cochin, 75014 Paris, France, University of Paris Descartes (Paris V), 75006 Paris, France, Department of Pathobiological Science and Technology, School of Health Science, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan, Division of Hematology and Oncology, St. Marianna University School of Medicine Hospital, Kawasaki, Kanagawa 216-8511, Japan, Department of Pathology, Okayama University Hospital, Okayama 700-8530, Japan, Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan
Published online on: October 24, 2014 https://doi.org/10.3892/or.2014.3567
Pages: 171-178

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Abstract

A cell line named PRU-1, derived from a Langerhans cell (LC) histiocytosis (LCH) skull lesion of a 7-year-old boy, was established and characterized. PRU-1 is an adherent spindle-shaped cell line that shows no Birbeck granules on electron microscopy. Flow cytometric analysis of cells collected from the early seventh passage showed no LC phenotypes of CD1a and S100 protein. Immunostaining of PRU-1 cells also revealed no expression of LC markers but showed expression of CD11c, CD54 (ICAM-1) and CD68, which was also observed in some peripherally located cells of the original LCH lesion. The PRU-1 cells stained positive for factor XIIIa and negative for CD34, suggesting a dermal dendritic cell phenotype. Cytogenetic analyses revealed abnormalities such as 39,XY,-2,-4,-8,-12,-12,-14,add(18)(q21),20,+mar and 44,XY,-11,-14,add(18)(q21). TCRγ rearrangement in the PRU-1 cells was not amplified by PCR. Tumorigenicity was not proven by xenografting into SCID mice. A conditioned medium from PRU-1 culture induced the proliferation of peripheral blood lymphocytes as well as the activation of monocytes from a healthy donor into CD1a-positive LC-like cells. Because the phenotypic characteristics of PRU-1 differed from those of CD1a-positive abnormal LC-like cells (LCH cells), it was likely that the PRU-1 cells were derived from peripherally located cells of the LCH lesion rather than LCH cells. LCH has been regarded as a type of granulomatous neoplasm with several intermingled inflammatory cells and influenced by stimuli such as Merkel cell polyomavirus (MCPyV) infection or cigarette smoking. However, in the PRU-1 cells, MCPyV-DNA was not detected by PCR. Stromal cell-like PRU-1 cells are likely to produce some growth or differentiation factors, which may play important roles in LCH lesion formation, cell maintenance and LC-like cell induction.

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1	Writing Group of the Histiocyte Society. Histiocytosis syndromes in children. Writing Group of the Histiocyte Society. Lancet. 1:208–209. 1987.PubMed/NCBI
2	Yousem SA, Dacic S, Nikiforov YE and Nikiforova M: Pulmonary Langerhans cell histiocytosis: profiling of multifocal tumors using next-generation sequencing identifies concordant occurrence of BRAF V600E mutations. Chest. 143:1679–1684. 2013. View Article : Google Scholar : PubMed/NCBI
3	Badalian-Very G, Vergilio JA, Degar BA, et al: Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood. 116:1919–1923. 2010. View Article : Google Scholar : PubMed/NCBI
4	Murakami I, Matsushita M, Iwasaki T, et al: Merkel cell polyomavirus DNA sequences in peripheral blood and tissues from patients with Langerhans cell histiocytosis. Hum Pathol. 45:119–126. 2014. View Article : Google Scholar
5	Sakata N, Toguchi N, Kimura M, Nakayama M, Kawa K and Takemura T: Development of Langerhans cell histiocytosis associated with chronic active Epstein-Barr virus infection. Pediatr Blood Cancer. 50:924–927. 2008. View Article : Google Scholar
6	Chen CJ, Ho TY, Lu JJ, et al: Identical twin brothers concordant for Langerhans’ cell histiocytosis and discordant for Epstein-Barr virus-associated haemophagocytic syndrome. Eur J Pediatr. 163:536–539. 2004. View Article : Google Scholar : PubMed/NCBI
7	Yousem SA, Colby TV, Chen YY, Chen WG and Weiss LM: Pulmonary Langerhans’ cell histiocytosis: molecular analysis of clonality. Am J Surg Pathol. 25:630–636. 2001. View Article : Google Scholar : PubMed/NCBI
8	Tazi A, Hiltermann JN and Vassallo R: Adult lung histiocytosis. Histiocytic Disorders of Children and Adults. Weitzman S and Egeler RM: Cambridge University Press; Cambridge: pp. 187–207. 2005
9	Corbeel L, Eggermont E, Desmyter J, et al: Spontaneous healing of Langerhans cell histiocytosis (histiocytosis X). Eur J Pediatr. 148:32–33. 1988. View Article : Google Scholar : PubMed/NCBI
10	Mogulkoc N, Veral A, Bishop PW, Bayindir U, Pickering CA and Egan JJ: Pulmonary Langerhans’ cell histiocytosis: radiologic resolution following smoking cessation. Chest. 115:1452–1455. 1999. View Article : Google Scholar : PubMed/NCBI
11	Von Essen S, West W, Sitorius M and Rennard SI: Complete resolution of roentgenographic changes in a patient with pulmonary histiocytosis X. Chest. 98:765–767. 1990. View Article : Google Scholar : PubMed/NCBI
12	Kawakubo Y, Kishimoto H, Sato Y, et al: Human cytomegalo-virus infection in foci of Langerhans cell histiocytosis. Virchows Arch. 434:109–115. 1999. View Article : Google Scholar : PubMed/NCBI
13	Leahy MA, Krejci SM, Friednash M, et al: Human herpesvirus 6 is present in lesions of Langerhans cell histiocytosis. J Invest Dermatol. 101:642–645. 1993. View Article : Google Scholar : PubMed/NCBI
14	Glotzbecker MP, Carpentieri DF and Dormans JP: Langerhans cell histiocytosis: a primary viral infection of bone? Human herpes virus 6 latent protein detected in lymphocytes from tissue of children. J Pediatr Orthop. 24:123–129. 2004. View Article : Google Scholar
15	Jenson HB, McClain KL, Leach CT, Deng JH and Gao SJ: Evaluation of human herpesvirus type 8 infection in childhood langerhans cell histiocytosis. Am J Hematol. 64:237–241. 2000. View Article : Google Scholar : PubMed/NCBI
16	Scappaticci S, Danesino C, Rossi E, et al: Cytogenetic abnormalities in PHA-stimulated lymphocytes from patients with Langerhans cell histocytosis. AIEOP-Istiocitosi Group. Br J Haematol. 111:258–262. 2000. View Article : Google Scholar : PubMed/NCBI
17	Gogusev J, Telvi L, Murakami I, et al: DOR-1, A novel CD10⁺ stromal cell line derived from progressive Langerhans cell histiocytosis of bone. Pediatr Blood Cancer. 44:128–137. 2005. View Article : Google Scholar
18	Van Dongen JJ, Langerak AW, Bruggemann M, et al: Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 17:2257–2317. 2003. View Article : Google Scholar : PubMed/NCBI
19	Kuwamoto S, Higaki H, Kanai K, et al: Association of Merkel cell polyomavirus infection with morphologic differences in Merkel cell carcinoma. Hum Pathol. 42:632–640. 2011. View Article : Google Scholar : PubMed/NCBI
20	Feldman AL, Berthold F, Arceci RJ, et al: Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis. Lancet Oncol. 6:435–437. 2005. View Article : Google Scholar : PubMed/NCBI
21	Nezelof C and Basset F: An hypothesis Langerhans cell histiocytosis: the failure of the immune system to switch from an innate to an adaptive mode. Pediatr Blood Cancer. 42:398–400. 2004. View Article : Google Scholar : PubMed/NCBI
22	Arenzana-Seisdedos F, Barbey S, Virelizier JL, Kornprobst M and Nezelof C: Histiocytosis X. Purified (T6⁺) cells from bone granuloma produce interleukin 1 and prostaglandin E2 in culture. J Clin Invest. 77:326–329. 1986. View Article : Google Scholar : PubMed/NCBI
23	Geissmann F, Lepelletier Y, Fraitag S, et al: Differentiation of Langerhans cells in Langerhans cell histiocytosis. Blood. 97:1241–1248. 2001. View Article : Google Scholar : PubMed/NCBI
24	Nezelof C and Basset F: Langerhans cell histiocytosis research. Past, present, and future. Hematol Oncol Clin North Am. 12:385–406. 1998. View Article : Google Scholar : PubMed/NCBI
25	Aiba S and Tagami H: Phorbol 12-myristate 13-acetate can transform monocyte-derived dendritic cells to different cell types similar to those found in dermatofibroma. A possible in vitro model of the histogenesis of dermatofibroma. J Cutan Pathol. 25:65–71. 1998. View Article : Google Scholar : PubMed/NCBI
26	Erlandson RA: Ultrastructural features of specific human neoplasms with clinicopathologic, immunohistochemical, and cytogenetic correlations. Diagnostic Transmission Electron Microscopy of Tumors. Raven Press; New York, NY: pp. 243–832. 1994
27	Weitzman S and Egeler RM: Langerhans cell histiocytosis of bone. Histiocytic Disorders of Children and Adults. Cambridge University Press; Cambridge: pp. 154–173. 2005, View Article : Google Scholar
28	Lu H, Chen J, Planko L, Zigrino P, Klein-Hitpass L and Magin TM: Induction of inflammatory cytokines by a keratin mutation and their repression by a small molecule in a mouse model for EBS. J Invest Dermatol. 127:2781–2789. 2007.PubMed/NCBI
29	Egeler RM, Favara BE, van Meurs M, Laman JD and Claassen E: Differential in situ cytokine profiles of Langerhans-like cells and T cells in Langerhans cell histiocytosis: abundant expression of cytokines relevant to disease and treatment. Blood. 94:4195–4201. 1999.PubMed/NCBI
30	Raushenbakh MO, Ivanova VD, Shevchenko VE, Makhonova LA and Sergeev AV: Congenital tyrosine metabolism disorders in children with hemoblastoses. Vestn Akad Med Nauk SSSR. 19–24. 1981.(In Russian).
31	Larrengina AT and Falo LD Jr: Dendritic cells in the context of skin immunity. Dendritic Cells. Lotze MT and Thomson AW: Academic Press; San Diego, CA: pp. 301–314. 2001, View Article : Google Scholar
32	Betts DR, Leibundgut KE, Feldges A, Pluss HJ and Niggli FK: Cytogenetic abnormalities in Langerhans cell histiocytosis. Br J Cancer. 77:552–555. 1998. View Article : Google Scholar : PubMed/NCBI
33	Murakami I, Gogusev J, Fournet JC, Glorion C and Jaubert F: Detection of molecular cytogenetic aberrations in langerhans cell histiocytosis of bone. Hum Pathol. 33:555–560. 2002. View Article : Google Scholar : PubMed/NCBI
34	Arico M, Nichols K, Whitlock JA, et al: Familial clustering of Langerhans cell histiocytosis. Br J Haematol. 107:883–888. 1999. View Article : Google Scholar : PubMed/NCBI
35	Dufour C, Lanciotti M, Micalizzi C, Valetto A and Haupt R: Non-identical twin sisters concordant for Langerhans cell histiocytosis and discordant for secondary acute promyelocytic leukemia. Med Pediatr Oncol. 37:70–72. 2001. View Article : Google Scholar : PubMed/NCBI
36	Enjolras O, Leibowitch M, Bonacini F, Vacher-Lavenu MC and Escande JP: Congenital cutaneous Langerhans histiocytosis. Apropos of 7 cases. Ann Dermatol Venereol. 119:111–117. 1992.(In French).
37	Miyatani K, Takahashi K, Yanai H, Yoshino T and Akagi T: Partial purification and characterization of dendritic cell differentiation factor. Acta Med Okayama. 48:67–72. 1994.PubMed/NCBI
38	Feng H, Shuda M, Chang Y and Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 319:1096–1100. 2008. View Article : Google Scholar : PubMed/NCBI