Heparanase and vascular endothelial growth factor expression in the progression of oral mucosal melanoma

Rivera, R.S.; Nagatsuka, H.; Siar, C.H.; Gunduz, M.; Tsujigiwa, H.; Han, P.P.; Katase, N.; Tamamura, R.; Ng, K.H.; Naomoto, Y.; Nakajima, M.; Nagai, N. (2008) Heparanase and vascular endothelial growth factor expression in the progression of oral mucosal melanoma. Oncology Reports, 19 (3). pp. 657-661. ISSN 1021-335X

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    Oral mucosal melanoma is an aggressive neoplasm with poor prognosis. Heparanase is an endo-beta-d-glucuronidase, which cleaves heparan sulphate chains. The vascular endothelial growth factor (VEGF) is the most potent angiogenic mitogen and interaction with its receptor (VEGFR) has been associated with angiogenesis. We investigated the expression of these molecules in the progression of oral mucosal melanoma. Immunohistochemistry was carried out in 15 oral melanotic macules and 19 oral melanomas using heparanase, VEGF, VEGFR-2, CD34 and Ki-67. Microvessel density was determined and subjected to statistical analysis. Heparanase and VEGFR-2 were not expressed in the oral melanotic macule. Atypical melanocytes and melanoma cells expressed heparanase, VEGF and VEGFR-2. An intense expression was noted in the early invasive phase, which marks the crucial transition from in situ to the invasive phase. In the invasive component, heparanase was intense but selective in the invasive fronts and at the periphery of nests unlike the extensive expression of VEGF and VEGFR-2. However, hot spots were only observed at the periphery of the nests. In conclusion, melanoma cells expressed heparanase, VEGF and VEGFR-2. The coexpression of these molecules in atypical melanocytes and melanoma cells suggests their function in cell migration and invasion. Moreover, the intense expression in the crucial transition from in situ to the invasive phase suggests their role in the progression of the tumor. The role of VEGF and VEGFR-2 in angiogenesis was evident only at the periphery of the nests in the invasive components.

    Item Type: Article
    1. Rivera, R.S.
    2. Nagatsuka, H.
    3. Siar, C.H.
    4. Gunduz, M.
    5. Tsujigiwa, H.
    6. Han, P.P.
    7. Katase, N.
    8. Tamamura, R.
    9. Ng, K.H.
    10. Naomoto, Y.
    11. Nakajima, M.
    12. Nagai, N.
    Journal or Publication Title: Oncology Reports
    Additional Information: ISI Document Delivery No.: 268EK Times Cited: 10 Cited Reference Count: 25 Cited References: Barker BF, 1997, ORAL SURG ORAL MED O, V83, P672, DOI 10.1016/S1079-2104(97)90318-8 De Jong JS, 1998, J PATHOL, V184, P53, DOI 10.1002/(SICI)1096-9896(199801)184:1<53::AID-PATH6>3.0.CO;2-7 Dome B, 2002, J PATHOL, V197, P355, DOI 10.1002/path.1124 Elkin M, 2001, FASEB J, V15, P1661, DOI 10.1096/fj.00-0895fje Erhard H, 1997, MELANOMA RES, V7, pS19 FOLKMAN J, 1992, J BIOL CHEM, V267, P10931 Foss AJE, 1996, CANCER RES, V56, P2900 Gingis-Velitski S, 2004, J BIOL CHEM, V279, P23536, DOI 10.1074/jbc.M400554200 Goldschmidt O, 2003, FASEB J, V17, P1015, DOI 10.1096/fj.02-0773com Hicks MJ, 2000, ORAL ONCOL, V36, P152, DOI 10.1016/S1368-8375(99)00085-8 Kato T, 1999, BREAST CANCER RES TR, V53, P19, DOI 10.1023/A:1006193024382 Lacal PM, 2005, INT J ONCOL, V27, P1625 Lee YJ, 2002, J HISTOCHEM CYTOCHEM, V50, P1555 Maniotis AJ, 1999, AM J PATHOL, V155, P739, DOI 10.1016/S0002-9440(10)65173-5 Mikami S, 2004, PATHOL INT, V54, P556, DOI 10.1111/j.1440-1827.2004.01664.x Nagatsuka H, 2005, VIRCHOWS ARCH, V447, P710, DOI 10.1007/s00428-005-0016-1 NAKAJIMA M, 1988, J CELL BIOCHEM, V36, P157, DOI 10.1002/jcb.240360207 Parish C.R., 2001, BIOCHIM BIOPHYS ACTA, V1471, P99 Pisacane AM, 2005, MELANOMA RES, V15, P39, DOI 10.1097/00008390-200502000-00007 Robinson CJ, 2001, J CELL SCI, V114, P853 SHALABY F, 1995, NATURE, V376, P62, DOI 10.1038/376062a0 Toyoshima M, 1999, J BIOL CHEM, V274, P24153, DOI 10.1074/jbc.274.34.24153 Vlodavsky I, 2001, J CLIN INVEST, V108, P341, DOI 10.1172/JCI13662 Zetser A, 2006, CANCER RES, V66, P1455, DOI 10.1158/0008-5472.CAN-05-1811 Zhang SW, 2006, ONCOL REP, V15, P15 Rivera, Rosario S. Nagatsuka, Hitoshi Siar, Chong Huat Gunduz, Mehmet Tsujigiwa, Hidetsugu Han, Phuu Pwint Katase, Naoki Tamamura, Ryo Ng, Kok Han Naomoto, Yoshio Nakajima, Motowo Nagai, Noriyuki Professor d a spandidos Athens
    Uncontrolled Keywords: Oral mucosal melanoma heparanase vascular endothelial growth factor vascular endothelial growth factor-receptor microvessel density breast-cancer angiogenesis metastasis activation receptors patterns survival cells vegf
    Subjects: R Medicine > RK Dentistry
    Divisions: Faculty of Dentistry > Dept of Oral Pathology & Oral Medicine & Periodontology
    Depositing User: Ms Nursyafiqah Abd Malek
    Date Deposited: 10 Jan 2013 08:15
    Last Modified: 10 Jan 2013 08:15
    URI: http://eprints.um.edu.my/id/eprint/4311

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