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Siar, C. H. and Ha, K. O. and Aung, L. O. and Nakano, K. and Tsujigiwa, H. and Nagatsuka, H. and Ng, K. H. and Kawakami, T. (2010) IMMUNOLOCALIZATION OF NOTCH SIGNALING PROTEIN MOLECULES IN A MAXILLARY CHONDROSARCOMA AND ITS RECURRENT TUMOR. European Journal of Medical Research, 15 (10). pp. 456-460. ISSN 0949-2321

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    Abstract

    Background: Notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified. Method: Tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) expression. Results: Both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I). Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members. Conclusions: Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.

    Item Type: Article
    Additional Information: ISI Document Delivery No.: 676FN Times Cited: 1 Cited Reference Count: 21 Cited References: Artavanis-Tsakonas S, 1999, SCIENCE, V284, P770, DOI 10.1126/science.284.5415.770 Fiuza UM, 2007, J ENDOCRINOL, V194, P459, DOI 10.1677/JOE-07-0242 Fletcher CD, 2002, PATHOLOGY GENETICS T Fortini ME, 2009, DEV CELL, V16, P633, DOI 10.1016/j.devcel.2009.03.010 Harper JA, 2003, CLIN GENET, V64, P461, DOI 10.1046/j.1399-0004.2003.00194.x Ijuin K, 2008, MECH DEVELOP, V125, P462, DOI 10.1016/j.mod.2008.01.008 KAWAKAMI T, 2004, EUR J MED RES, V9, P1 Kawakami T, 2005, EUR J MED RES, V10, P475 Koch BB, 2000, HEAD NECK-J SCI SPEC, V22, P408, DOI 10.1002/1097-0347(200007)22:4<408::AID-HED15>3.0.CO;2-H Leong KG, 2006, BLOOD, V107, P2223, DOI 10.1182/blood-2005-08-3329 Masuya M, 2002, INT J HEMATOL, V75, P269, DOI 10.1007/BF02982040 Miele L, 2006, CLIN CANCER RES, V12, P1074, DOI 10.1158/1078-0432.CCR-05-2570 Mohammadinezhad C, 2009, J CRANIOFAC SURG, V20, P2097, DOI 10.1097/SCS.0b013e3181bec5d3 Nakano K, 2008, EUR J MED RES, V13, P476 NAKANO K, 2008, J HARD TISSUE BIOL, P79 Oldershaw RA, 2010, BONE, V46, P286, DOI 10.1016/j.bone.2009.04.242 Prado FO, 2009, BRIT J ORAL MAX SURG, V47, P555, DOI 10.1016/j.bjoms.2009.05.012 Saini R, 2007, J CAN DENT ASSOC, V73, P175 SHIRATO T, 2006, ORAL ONCOL, V43, P247 Siar CH, 2010, EUR J MED RES, V15, P180 Van Damme PA, 2005, INT J ORAL MAX SURG, V34, P94, DOI 10.1016/j.ijom.2004.02.011 Siar, C. H. Ha, K. O. Aung, L. O. Nakano, K. Tsujigiwa, H. Nagatsuka, H. Ng, K. H. Kawakami, T. University of MalayaRG083/09HTM; Japan Society for the Promotion of Science20592349 This study was partially funded by the University of Malaya Research Grant (RG083/09HTM) and Grant-in-aid for Scientific Research (C) (20592349) from the Japan Society for the Promotion of Science. I holzapfel verlag gmbh Munich
    Uncontrolled Keywords: Chondrosarcoma Immunohistochemistry Notch receptors Notch ligands cells
    Subjects: Medicine and Dentistry > Clinical Dentistry
    Divisions: UNSPECIFIED
    Depositing User: Ms Nursyafiqah Abd Malek
    Date Deposited: 30 Oct 2012 03:03
    Last Modified: 30 Oct 2012 03:03
    URI: http://opendepot.org/id/eprint/1497

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