Top

Clinical Orthopaedics and Related Research®

Published in:

01-09-2008 | Symposium: Molecular Genetics in Sarcoma

Histogenetic Characterization of Giant Cell Tumor of Bone

Authors: Manuela Salerno, MSc, Sofia Avnet, PhD, Marco Alberghini, MD, Armando Giunti, MD, Nicola Baldini, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 9/2008

Abstract

The unpredictable behavior of giant cell tumor (GCT) parallels its controversial histogenesis. Multinucleated giant cells, stromal cells, and CD68⁺ monocytes/macrophages are the three elements that interact in GCT. We compared the ability of stromal cells and normal mesenchymal stromal cells to differentiate into osteoblasts. Stromal cells and mesenchymal cells had similar proliferation rates and lifespans. Although stromal cells expressed early osteogenic markers, they were unable to differentiate into osteoblasts but they did express intracellular adhesion molecule-1, a marker of bone-lining cells. They were unable to form clones in a semisolid medium and unable to promote osteoclast differentiation, although they exerted a strong chemotactic effect on osteoclast precursors. Stromal cells may be either immature proliferating osteogenic elements or specialized osteoblast-like cells that fail to show neoplastic features but can induce the differentiation of osteoclast precursors. They might be secondarily induced to proliferate by a paracrine effect induced by monocyte-macrophages and/or giant cells. The increased number of giant cells in GCT may be secondary to an autocrine circuit mediated by the receptor activator of nuclear factor kB.

Athanasou NA, Bliss E, Gatter KC, Heryet A, Woods CG, McGee JO. An immunohistological study of giant-cell tumour of bone: evidence for an osteoclast origin of the giant cells. J Pathol. 1985;147:153–158.PubMedCrossRef

Bauer FC, Urist MR. The reaction of giant cell tumors of bone to transplantation into athmic mice: including observations on osteoinduction in the host bed. Clin Orthop Relat Res. 1981;159:257–264.PubMed

Bertoni F, Present D, Sudanese A, Baldini N, Bacchini P, Campanacci M. Giant-cell tumor of bone with pulmonary metastases: six case reports and a review of the literature. Clin Orthop Relat Res. 1988;237:275–285.PubMed

Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998;279:349–352.PubMedCrossRef

Brien EW, Mirra JM, Kessler S, Suen M, Ho JK, Yang WT. Benign giant cell tumor of bone with osteosarcomatous transformation (‘dedifferentiated’ primary malignant GCT): report of two cases. Skeletal Radiol. 1997;26:246–255.PubMedCrossRef

Boriani S, Sudanese A, Baldini N, Picci P. Sarcomatous evolution of giant cell tumor. Ital J Orthop Traumatol. 1986;12:203–211.

Cameron JAP, Marsden ATH, Lumpur K. Malignant osteoclastoma. J Bone Joint Surg Br. 1952;34:93–96.PubMed

Campanacci M, Baldini N, Boriani S, Sudanese A. Giant-cell tumor of bone. J Bone Joint Surg Am. 1987;69:106–113.PubMed

Campanacci M, Giunti A, Olmi R. Giant-cell tumours of bone. A study of 209 cases with long-term follow-up in 130. Ital J Orthop Traumatol. 1975;1:153–180.

10.

D’Amelio P, Grimaldi A, Pescarmona GP, Tamone C, Roato I, Isaia G. Spontaneous osteoclast formation from peripheral blood mononuclear cells in postmenopausal osteoporosis. FASEB J. 2004;19:410–412.PubMed

11.

Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cfba1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747–754.PubMedCrossRef

12.

Everts V, Delaissè JM, Korper W, Janses DC, Tighcelaar-Gutter W, Safting P, Beertsen A. The bone lining cell: its role in cleaning Howship’s lacunae and initiating bone formation. J Bone Miner Res. 2002;17:77–90.PubMedCrossRef

13.

Gamberi G, Benassi MS, Bohling T, Ragazzini P, Molendini L, Sollazzo MR, Merli M, Ferrari C, Magagnoli G, Bertoni F, Picci P. Prognostic relevance of C-myc gene expression in giant-cell tumor of bone. J Orthop Res. 1998,16:1–7.PubMedCrossRef

14.

Goldring SR, Roelke MS, Petrison KK, Bhan AK. Human giant cell tumors of bone identification and characterization of cell types. J Clin Invest. 1987;79:483–491.PubMedCrossRef

15.

Granchi D, Amato I, Battistelli L, Avnet S, Capaccioli S, Papucci L, Donnini M, Pellacani A, Brandi ML, Giunti A, Baldini N. In vitro blockade of receptor activator of nuclear factor-kb ligand prevents osteoclastogenesis induced by neuroblastoma cells. Int J Cancer. 2004;111:829–838.PubMedCrossRef

16.

Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab. 2006;52:499–509.PubMed

17.

Harada H, Tagashira S, Fujivara M, Ogawa S, Katsumata T, Yamaguchi A, Komori T, Nakatsuka M. Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem. 1999;274:6927–6928.CrossRef

18.

Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res. 2000;15:2–12.PubMedCrossRef

19.

Huang L, Teng XY, Cheng YY, Lee KM, Kumta SM. Expression of preosteoblast markers and Cbfa1 and Osterix gene transcripts in stromal tumour cells of giant cell tumour of bone. Bone. 2004;34:393–401.PubMedCrossRef

20.

Huang L, Xu J, Wood JD, Zeng MH. Gene expression of osteoprotegerin ligand, osteoprotegerin, and receptor activator of NF-kB in giant cell tumor of bone. Am J Pathol. 2000;156:761–767.PubMed

21.

Huang TS, Green AD, Beattie CW, Das Gupta TK. Monocyte-macrophage lineage of giant cell tumor of bone. Establishment of a multinucleated cell line. Cancer. 1993;71:1751–1760.PubMedCrossRef

22.

Husheem M, Nyman JK, Vääräniemi J, Vaanenen HK, Hentunen TA. Characterization of circulating human osteoclast progenitors: development of in vitro resorption assay. Calcif Tissue Int. 2005;76:222–230.PubMedCrossRef

23.

Jaffe JL, Lichtenstein L, Portis RB. Giant cell tumor of bone: its pathologic appearance, grading, supposed variants and treatment. Arch Pathol. 1940;30:993–1031.

24.

Joyner CJ, Quinn JM, Triffitt JT, Owen ME, Athanasou NA. Phenotypic characterisation of mononuclear and multinucleated cells of giant cell tumour of bone. Bone Miner. 1992;16:37–48.PubMedCrossRef

25.

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755–764.PubMedCrossRef

26.

Kulterer B, Friedl G, Jandrositz A, Sanchez-Cabo F, Prokesch A, Paar C, Scheideler M, Windhager R, Preisegger KH, Trajanoski Z. Gene expression profiling of human mesenchymal stem cells derived from bone marrow during expansion and osteoblast differentiation. BMC Genomics. 2007;8:70–84.PubMedCrossRef

27.

Kusuzaki K, Takeshita H, Murata H, Hashiguchi S, Nozaki T, Emoto K, Ashihara T, Hirasawa Y. Relationship between binucleated and multinucleated cells in giant cell tumor of bone. Anticancer Res. 2000;20:2463–2468.PubMed

28.

Lau YS, Sabokbar A, Gibbons CL, Giele H, Athanasou N. Phenotypic and molecular studies of giant-cell tumors of bone and soft tissue. Hum Pathol. 2005:36:945–954.PubMedCrossRef

29.

Liao TS, Yurgelun MB, Chang SS, Zhang HZ, Murakami K, Blaine TA, Parisien MV, Kim W, Winchester RJ, Lee FYL. Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. J Orthop Res. 2005;23:203–209.PubMedCrossRef

30.

Lindeman JHN, Hanemaaijer R, Mulder A, Dijkstra S, Szuhai K, Bromme D, Verheijen JH, Hogendoorn PC. Cathespin K is the principal protease in giant cell tumor of bone. Am J Pathol. 2004;165:593–601.PubMed

31.

Mankin HJ, Connor JF, Schiller AL, Perlmutter N, Alho A, McGuire M. Grading of bone tumors by analysis of nuclear DNA content using flow cytometry. J Bone Joint Surg Am. 1985;67:404–413.PubMed

32.

Marletta G, Ciapetti G, Satriano C, Perut F, Salerno M, Baldini N. Improved osteogenic differentiation of human marrow stromal cells cultured on ion-induced chemically structured poly-epsilon-caprolactone. Biomaterials. 2007;28:1132–1140.PubMedCrossRef

33.

Mathon AN, Lloyd AC. Cell senescence and cancer. Nat Rev Cancer. 2001;1:203–213.PubMedCrossRef

34.

Miyamoto N, Higuchi Y, Takima M, Ito M, Tsurudome M, Nishio M, Kawano M, Sudo A, Uchida A, Ito Y. Spindle-shaped cells derived from giant-cell tumor of bone support differentiation of blood monocytes to osteoclast-like cells. J Orthop Res. 2000;18:647–654.PubMedCrossRef

35.

Morgan T, Atkins GJ, Trivett MK, Johnson SA, Kansara M, Schlicht SL, Slavin JL, Simmons P, Dickinson I, Powell G, Choong PF, Holloway AJ, Thomas DM. Molecular profiling of giant cell tumor of bone and the osteoclastic localization of ligand for receptor activator of nuclear factor kappaB. Am J Pathol. 2005;167:117–128.PubMed

36.

Murata A, Fujita T, Kawahara N, Tsuchiya H, Tomita K. Osteoblast lineage properties in giant cell tumors of bone. J Orthop Sci. 2005;10:581–588.PubMedCrossRef

37.

Nicholson GC, Malakellis M, Collier FM, Cameron PU, Holloway WR, Gough TJ, Gregorio-King C, Kirkland MA, Myers DE. Induction of osteoclasts from CD14-positive human peripheral blood mononuclear cells by receptor activator of nuclear factor kappaB ligand (RANKL). Clin Sci. 2000;99:133–140.PubMedCrossRef

38.

Nishimura M, Yuasa K, Mori K, Miyamoto N, Ito M, Tsurudome M, Nishio M, Kawano M, Komada H, Uchida A, Ito Y. Cytological properties of stromal cells derived from giant cell tumor of bone (GCTSC) which can induce osteoclast formation of human blood monocytes without cell to cell contact. J Orthop Res. 2005;23:979–987.PubMedCrossRef

39.

O’Donnell RJ, Springfield DS, Motwani HK, Ready JE, Gebhardt MC, Mankin HJ. Recurrence of giant cell tumors of the long bones after curettage and packing with cement. J Bone Joint Surg Am. 1994;76:1827–1833.PubMed

40.

Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322.PubMedCrossRef

41.

Schuffstall RM, Gregory JE. Osteoid formation in giant cell tumours of bone. Am J Pathol. 1953;29:1113–1131.

42.

Scotlandi K, Serra M, Manara C, Maurici D, Benini S, Nini G, Campanacci M, Baldini N. Clinical relevance of Ki-67 expression in bone tumors. Cancer. 1995;75:806–814.PubMedCrossRef

43.

Tanaka Y, Maruo A, Kujii K, Nomi M, Nakamura T, Eto S, Minami Y. Intercellular adhesion molecule 1 discriminates functionally different populations of human osteoblasts: characteristic involvement of cell cycle regulators. J Bone Miner Res. 2000;15:1912–1923.PubMedCrossRef

44.

Tanaka Y, Mine S, Hanagiri T, Hiraga T, Morimoto I, Figdor CG, van Kooyk Y, Ozawa H, Nakamura T, Yasumoto K, Eto S. Constitutive up-regulation of integrin-mediated adhesion of tumor-infiltrating lymphocytes to osteoblasts and bone marrow-derived stromal cells. Cancer Res. 1998;58:4138–4145.PubMed

45.

Tanaka Y, Morimoto I, Nakano Y, Okada Y, Hirota S, Nomura S, Nakamura T, Eto S. Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1. J Bone Miner Res. 1995;10:1462–1469.PubMedCrossRef

46.

Wulling M, Delling G, Kaiser E. The origin of the neoplastic stromal cell in giant cell tumor of bone. J Cancer Res Clin Oncol. 2001;34:983–993.

47.

Zheng MH, Robbins P, Xu J, Huang L, Wood DJ, Papadimitriou JM. The histogenesis of giant cell tumour of bone: a model of interaction between neoplastic cells and osteoclasts. Histol Histopathol. 2001;16:297–307.PubMed

48.

Zheng MH, Siu P, Papadimitriou JM, Wood DJ, Murch AR. Telomeric fusion is a major cytogenetic aberration of giant cell tumors of bone. Pathology. 1999;31:373–378.PubMedCrossRef

Title: Histogenetic Characterization of Giant Cell Tumor of Bone
Authors: Manuela Salerno, MSc
Sofia Avnet, PhD
Marco Alberghini, MD
Armando Giunti, MD
Nicola Baldini, MD
Publication date: 01-09-2008
Publisher: Springer-Verlag
Published in: Clinical Orthopaedics and Related Research® / Issue 9/2008
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-008-0327-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Histogenetic Characterization of Giant Cell Tumor of Bone

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2008

Osteosarcoma Development and Stem Cell Differentiation

Case Reports: Splenic Rupture after Anterior Thoracolumbar Spinal Fusion Through a Thoracoabdominal Approach

Thigh Pain of 5 Years’ Duration in a 48-year-old Man

50 Years Ago in CORR: Heredity as a Factor in Malignancy H. Winnett Orr MD CORR 1956;8:142–146

Patients with Isolated Musculoskeletal Trauma Have Lower Mental Status Scores

Metastatic Osteosarcoma Gene Expression Differs In Vitro and In Vivo