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Immunohistochemical evaluation of cartilage-derived morphogenic protein-1 and -2 in normal human salivary glands and pleomorphic adenomas

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Abstract

Cartilage-derived morphogenic protein (CDMP)-1 and -2 belong to the bone morphogenetic protein (BMP) family in the transforming growth factor (TGF)-β superfamily. CDMP-1 and CDMP-2 were reported to play essential roles in limb cartilage and limb-joint formation in developing mice. Although pleomorphic adenoma of the salivary glands is an epithelial tumor, it frequently shows ectopic cartilaginous formation. These findings suggested that CDMP-1 and -2 may play essential roles in chondroid formation in salivary pleomorphic adenoma. To evaluate this hypothesis, we examined the expression and localization of CDMP-1 and -2 immunohistochemially in 20 normal human salivary glands and 35 pleomorphic adenomas. CDMP-1 was immunolocalized in the striated ducts and the intercalated ducts in the normal salivary glands. CDMP-1 was immunolocalized in the cuboidal neoplastic myoepithelial cells around the chondroid areas of the pleomorphic adenomas, whereas these molecules were not localized in the spindle-shaped neoplastic myoepithelial cells of the myxoid element or the lacuna cells of the chondroid element in these tumors. CDMP-2 was expressed neither in normal salivary glands nor any of the elements of the pleomorphic adenomas. Type-II collagen and aggrecan were immunolocalized throughout the matrix around the lacuna cells of the chondroid element, whereas type-X collagen was not immunlocalized in any epithelial or stromal elements, including the chondroid elements. Aggrecan was deposited not only on the chondroid matrix, but also on the myxoid stroma and intercellular spaces of the tubulo-glandular structures, whereas chondromodulin-I was deposited on the chondroid matrix. These results indicated that the cuboidal neoplastic myoepithelial cells around the chondroid areas expressed CDMP-1 and suggested that this molecule may play a role in the differentiation of neoplastic myoepithelial cells in pleomorphic adenoma. The phenotype of the lacuna cells was similar to that of mature to upper hypertrophic chondrocytes of the authentic cartilage. In conclusion, pleomorphic adenoma expressed CDMP-1 but not CDMP-2.

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References

  1. Chang CS, Hoang B, Thomas JT, Vukicevic S, Luyten PF, Ryba JPN, Kozak AC, Reddi AH, Moos M Jr (1994) Cartilage-derived morphogenetic proteins: new members of the transforming growth factor-β superfamily predominantly expressed in long bone during human embryonic development. J Biol Chem 269:28227–28234

    CAS  PubMed  Google Scholar 

  2. Dardick I (1996) Pleomorphic adenoma (benign mixed tumor) (chapter 9). In: Color atlas/text of the salivary gland tumor pathology. Igaku-Shoin Inc, New York, pp 75–92

  3. Erlacher L, McCartney J, Piek E, ten-Dijke P, Yanagishita M, Oppermann H, Luyten FP (1998) Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis. J Bone Miner Res 13:383–392

    CAS  PubMed  Google Scholar 

  4. Erlacher L, Ng C-K, Ullrich R, Krieger S, Luyten FP (1998) Presence of cartilage-derived morphogenetic proteins in articular cartilage and enhancement of matrix replacement in vitro. Arthritis-Rheum 41:263–273

    Article  CAS  Google Scholar 

  5. Folkman J, Klangsburn M (1967) Angiogenic factors. Science 235:442–447

    Google Scholar 

  6. Helder MN, Ozkaynak E, Sampath TK, Luyten FP, Latin V, Oppermann H, Vukicevic S (1995) Expression pattern of osteogenic protein-1 (bone morphogenetic protein-7) in human and mouse development. J Histochem Cytochem 43:1035–1044

    CAS  PubMed  Google Scholar 

  7. Hiraki Y, Tanaka H, Inoue H, Kondo J, Kmizono A, Suzuki F (1991) Molecular cloning of a new class of cartilage-specific matrix, chondromodulin-I, which stimulates growth of cultured chondrocytes. Biochem Biophys Res Commun 175:971–977

    CAS  PubMed  Google Scholar 

  8. Hiraki Y, Inoue H, Iyama K, Kamizono A, Ochiai M, Shukunami C, Iijima S, Suzuki F, Kondo J (1997) Identification of chondromodulin-I as a novel endothelial growth inhibitor: purification and its localization in the avascular zone of epiphyseal cartilage. J Biol Chem 272:32419–32426

    Article  CAS  PubMed  Google Scholar 

  9. Hiraki Y, Kono T, Sato M, Shukunami C, Kondo J (1997) Inhibition of DNA synthesis and tube morphogenesis of cultured vascular endothelial cells by chondromodulin-I. FEBS Lett 425:321–324

    Article  Google Scholar 

  10. Hiraki Y, Mitsui K, Endo N, Takahashi K, Hayami T, Inoue H, Shukunami C, Tokunaga K, Kono T, Yamada M, Takahashi HE, Kondo J (1999) Molecular cloning of human chondromodulin-I, a cartilage-derived growth modulating factor, and its expression in Chinese hamster ovary cells. Eur J Biochem 260:869–878

    Article  CAS  PubMed  Google Scholar 

  11. Hotten GC, Matsumoto T, Kimura M, Bechtold RF, Kron R, Ohara T, Tanaka H, Satoh Y, Okazaki M, Shirai T, Pan H, Kawai S, Pohl JS, Kudo A (1996) Recombinant human growth/differentiation factor 5 stimulates mesenchyme aggregation and chondrogenesis responsible for the skeletal development. Growth Factors 13:65–74

    CAS  PubMed  Google Scholar 

  12. Kusafuka K, Yamaguchi A, Kayano T, Fujuwara M, Takemura T (1998) Expression of bone morphogenetic proteins in salivary pleomorphic adenomas. Virchows Arch 432:247–253

    Article  CAS  PubMed  Google Scholar 

  13. Kusafuka K, Yamaguchi A, Kayano T, Takemura T (1998) Immunohistochemical localization of fibroblast growth factors (FGFs) and FGF receptor-1 in human normal salivary glands and pleomorphic adenomas. J Oral Pathol Med 27:287–292

    Google Scholar 

  14. Kusafuka K, Yamaguchi A, Kayano T, Takemura T (1999) Immunohistochemical localization of bone morphogenetic protein-6 in salivary pleomorphic adenomas. Pathol Int 49:1023–1027

    Article  CAS  PubMed  Google Scholar 

  15. Kusafuka K, Hiraki Y, Shukunami C, Yamaguchi A, Kayano T, Takemura T (2001) Cartilage-specific matrix protein chondormodulin-I is associated with chondroid formation in salivary pleomorphic adenomas: immunohistochemical analysis. Am J Pathol 158:1465–1472

    CAS  PubMed  Google Scholar 

  16. Luo W, Guo C, Zhang J, Chen TL, Wang PY, Vertel BM, Tanzer ML (2000) Aggrecan from start to finish. J Bone Miner Metab 18:51–56

    Article  CAS  PubMed  Google Scholar 

  17. Luyten FP (1997) Cartilage-derived morphogenetic protein-1. Int J Biochem Cell Biol 29:1241–1244

    Article  CAS  PubMed  Google Scholar 

  18. Lyons KM, Pelton RW, Hogan BLM (1989) Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor-β-like genes coordinately regulate aspects of embryonic development. Genes Dev 3:1657–1668

    CAS  PubMed  Google Scholar 

  19. Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, Yamashita H, Enomoto S, Miyazono K (1996) Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. J Biol Chem 271:21345–21352

    Article  CAS  PubMed  Google Scholar 

  20. Schmid TM, Popp RG, Linsenmayer TF (1990) Hypertrophic cartilage matrix: type X collagen, supramolecular assembly and calcification. Ann N Y Acad Sci 580:64–73

    CAS  PubMed  Google Scholar 

  21. Schmid TM, Bonen DK, Luchene L, Linsenmayer TF (1991) Late events in chondrocyte differentiation: hypertrophy, type X collagen synthesis and matrix calcification. In Vivo 5:533–540

    CAS  PubMed  Google Scholar 

  22. Shukunami C, Iyama K, Inoue H, Hiraki Y (1999) Spatiotemporal pattern of the mouse chondromodulin-I gene expression and its regulatory role in vascular invasion into cartilage during endochondral bone formation. Int J Dev Biol 43:39–49

    CAS  PubMed  Google Scholar 

  23. Takeda M, Iwata H, Suzuki S, Brown KS, Kimata K (1986) Correction of abnormal matrix formed by cmd/cmd chondrocytes in culture by exogenously added cartilage proteoglycan. J Cell Biol 103:1605–1614

    CAS  PubMed  Google Scholar 

  24. Zhao M, Takata T, Ogawa I, Yada T, Kimata K, Nikai H (1999) Immunohistochemical evaluation of the small and large proteoglycans in pleomorphic adenoma of the salivary glands. J Oral Pathol Med 28:37–42

    CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Susumu Sekiguchi, Kikuo Wakamatsu, Shoichi Hashimoto, Akira Niizeki, Hiroko Komatsuzaki and Eiji Shimada on the staff of the Department of Pathology, Japanese Red Cross Medical Center, Tokyo, Japan, for technical assistance. We wish to thank Mr. Takashi Yoshizawa at the Photo Studio, Tokyo Medical and Dental University, Tokyo, Japan, for microphotography. We also wish to thank Drs. Toshikazu Yada and Koji Kimata (Institute for Molecular Science of Medicine, Aichi Medical University, Nagoya, Japan) for generously providing specific antibody against aggrecan.

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Authors and Affiliations

  1. Department of Pathology, Japanese Red Cross Medical Center, 4-1-22 Hiroo, 150-8935, Tokyo , Japan

    Kimihide Kusafuka & Tamiko Takemura

  2. Laboratory for Skeletal Development and Joint Disorders, Katholieke Universiteit Leuven, Onderwijs & Navorsing, Herestraat 49, 8th floor, 3000 , Leuven, Belgium

    Franck P. Luyten & Raymond De Bondt

  3. Department of Molecular Interaction and Tissue Engneering, Institute for Frontier Sciences, Kyoto University, 53 Shogoinkawahara-cho, Sakyo-ku, 606-8507, Kyoto , Japan

    Yuji Hiraki & Chisa Shukunami

  4. Forensic Dentistry, Department of International Health Development, Division of Public Health, Graduate School, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, 113-8549, Tokyo , Japan

    Teruo Kayano

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  1. Kimihide Kusafuka
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  2. Franck P. Luyten
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  3. Raymond De Bondt
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  4. Yuji Hiraki
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  5. Chisa Shukunami
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  6. Teruo Kayano
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  7. Tamiko Takemura
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Correspondence to Kimihide Kusafuka.

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Kusafuka, K., Luyten, F.P., De Bondt, R. et al. Immunohistochemical evaluation of cartilage-derived morphogenic protein-1 and -2 in normal human salivary glands and pleomorphic adenomas. Virchows Arch 442, 482–490 (2003). https://doi.org/10.1007/s00428-003-0761-y

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  • DOI: https://doi.org/10.1007/s00428-003-0761-y

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