EXPRESSION OF THE GENES OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND VON WILLEBRAND FACTOR IN SALIVARY GLAND TUMORS

타액선 종양에서 혈관내피성장인자와 von Willebrand 인자 유전자 발현에 관한 연구

  • Chung, Ji-Hun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Kim, Ji-Hyuk (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Park, Young-Wook (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University)
  • 정지훈 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 김지혁 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 박영욱 (강릉대학교 치과대학 구강악안면외과학교실)
  • Published : 2008.01.31

Abstract

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor which compromises about 6$\sim$8% of all tumors followed by the adenoid cystic carcinoma (ACC) and adenocarcinoma. Most deaths from salivary carcinomas are caused by recurrent or metastatic lesions that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the vascular metastasis is important for the design of more effective therapy of salivary carcinomas. Neoangiogenesis is essential for tumor growth, which is postulated to be fundamentally dependent on the induction of stromal neovascularization. However, how neovascularization takes place in live tissue has not been fully established, especially in recruitment and differentiation of endothelial cells in the salivary gland tumors. Vascular endothelial growth factor (VEGF) is a heparin-binding, dimeric polypeptide growth factor known to exert its mitogenic activity specifically on endothelial cells. VEGF has been shown th be directly involved in angiogenesis, which in essential for the pathogenesis of many solid tumors. von Willebrand factor (vWF) is a large multimeric protein synthesized by megakaryocytes and endothelial cells that enable platelets to adhere to exposed subendothelium and, as well, to respond to changes in the blood flow. Recent studies suggest that increased levels of vWF correlate with progression of disease, metastasis, or survival time and thus may have a prognostic significance. vWF is explained as an acute phase proteins which is increased in cancer or as a result of increased endothelial cell synthesis associated with tumor-induced angiogenesis. Due to adhesive properties of vWF, its increased concentrations may also contribute metastasis of tumor. In this study, we determined the mRNA expression of VEGF and vWF in salivary ACC, MEC and pleomorphic adenoma by in situ hybridization. As a result, stronger expression of VEGF and vWF was seen in salivary ACC and MEC which has more invasive nature than the salivary benign tumor.

Keywords

References

  1. Katherine T, John D, Fotis I et al : Management of adenoid cystic carcinoma of minor salivary glands. J Oral Maxillofac Surg 64 : 1114, 2006 https://doi.org/10.1016/j.joms.2005.06.017
  2. Fan X, Yincheng Z, Feng L et al : Expression of IgSF in salivery adenoid cystic carcinoma and its relationship with invasion and metastasis. J Oral Patho Med 34 : 295, 2005 https://doi.org/10.1111/j.1600-0714.2005.00312.x
  3. Alfro JT, Andre DN, Priscila PCA et al : Management of salivary gland adenoid cystic carcinoma: institutional experience of a case series. Sao Paulo Med J 124(1) : 26, 2006 https://doi.org/10.1590/S1516-31802006000100006
  4. Son CW, Kim KW, Kim CH : Study on Expression of glycosaminoglycan in adenoid cystic carcinoma. J Kor Oral Maxillofac Surg 30 : 271, 2004
  5. Park YW : Celluar and molecular characterization of adenoid cyctic carcinoma of the salivary glands. J Kor Assoc Of Maxillofac Plast And Reconstr Surg 27(2) : 110, 2005
  6. Raguse JD, Gath HJ, Bier J et al : Docetaxel (taxotere) in recurrent high grade mucoepidermoid carnicoma of the major salivary glands. Oral Oncology EXTRA 40 : 5, 2004 https://doi.org/10.1016/S1741-9409(03)00003-7
  7. Bell BR, Dierks EJ, Homer L et al : Management and outmoce of patients with malignant salivary gland tumors. J Oral Maxillofac Surg 63 : 917, 2005 https://doi.org/10.1016/j.joms.2005.03.006
  8. Yih WY, Kratochvil EJ, Stewart CB : Intraoral minor salivary gland neoplasms: review of 213 cases. J Oral Maxillofac Surg 63 : 805, 2005 https://doi.org/10.1016/j.joms.2005.02.021
  9. Bhattacharyya N : Survival and prognosis for cancer of the submandibular gland. J Oral Maxillofac Surg 62 : 427, 2004 https://doi.org/10.1016/j.joms.2003.06.012
  10. Perez DEC, Pires FR, Lopes MA et al : Adenoid cystic carcinoma and mucoepidermoid carcinoma of the maxillary sinus: report of a 44-year experience of 25 cases from a single institution. J Oral Maxillofac Surg 64 : 1592, 2006 https://doi.org/10.1016/j.joms.2005.11.088
  11. Baj A, Bertolini F, Ferrari S et al : Central mucoepidermoid carcinoma of the jaw in a teenager: a case report. J Oral Maxillofac Surg 60 : 207, 2002 https://doi.org/10.1053/joms.2002.29827
  12. Sidoni A, Derrico P, Simoncelli C et al : Central mucoepidermoid carcinoma of the mandible: report of a case treated 13 years after first radiographic demonstration. J Oral Maxillofac Surg 54 : 1242, 1996 https://doi.org/10.1016/S0278-2391(96)90361-4
  13. Ishibashi H, Shiratuchi T, Nakagawa K et al : Hypoxiainduced angiogenesis of cultured human salivary gland carcinoma cells enhances vascular endothelial growth factor production and basic fibroblast growth factor release. Oral Oncol 37 : 77, 2001 https://doi.org/10.1016/S1368-8375(00)00062-2
  14. Weal S, Hiroko IY, Takashi S : Angiogenesis in mucous retention cyst: a human in vivo-like model of endothelial cell differentiation in mucous substrate. J Oral Pathol Med 34 : 30, 2005 https://doi.org/10.1111/j.1600-0714.2004.00282.x
  15. Lim JJ, Kang SM, Lee MR et al : Expression of vascular endothelial growth factor in salivary gland carcinomas and its relation to p53, Ki-67 and prognosis. J Oral Pathol Med 32 : 552, 2003 https://doi.org/10.1034/j.1600-0714.2003.00145.x
  16. Peter AB, Tijjani U, Alan WW et al : Expression of type 2 nitric oxide synthase and vascular endothelial growth factor in oral dysplasia. J Oral Maxillofac Surg 60 : 1455, 2002 https://doi.org/10.1053/joms.2002.36122
  17. Shang ZJ, Li JR, Li ZB : Upregulation of serum and tissue vascular endothelial growth factor correlates with angiogenesis and prognosis of oral squamous cell carcinoma. J Oral Maxillofac Surg 65 : 17, 2007
  18. Wong YK, Liu CJ, Kwan PC et al : Microvascular density and vascular endothelial growth factor immunoreactivity as predictors of regional lymph node metastasis from betelassociated oral squamous cell carcinoma. J Oral Maxillofac Surg 61 : 1257, 2003 https://doi.org/10.1016/S0278-2391(03)00725-0
  19. Schmugge M, Rand ML, Freedman J : Platelets and von willebrand factor. Transfusion and Apheresis Science 28 : 269, 2003 https://doi.org/10.1016/S1473-0502(03)00046-6
  20. Shavit JA, Motto DG : Coagulation and metastasis - an unexpected role for von Villebrand factor. J Thromb Heamost 4 : 517, 2006 https://doi.org/10.1111/j.1538-7836.2006.01805.x
  21. Paczuski R, Bialkowska A, Kotschy M et al : Von villebrand factor in plasma of patients with advanced stages of larynx cancer. Thrombosis Research 95 : 197, 1999 https://doi.org/10.1016/S0049-3848(99)00041-9
  22. Zavero MR : Structure of von villebrand factor and its function in platelet adhesion and thrombus formation. Best Practice & Research Clinical Heamatology 14(2) : 257, 2001 https://doi.org/10.1053/beha.2001.0133
  23. Teo NB, Shoker BS, Jarvis C et al : Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast. European Journal of Cancer 39 : 38, 2003 https://doi.org/10.1016/S0959-8049(02)00248-4
  24. Kikaku G : Immunohistochemistry. Gakusai Kikaku Co, 2002, p.297
  25. Lee SK, Kim YS, Song IS et al : Improved technique of digoxigenin labeled RNA in situ hybridization. The Korean Journal of Pathology 35 : 98, 2001
  26. Bhat TA, Singh RP : Tumor angiogenesis - a potential target in cancer chemoprevention. Food Chem Toxicol : 1, 2007
  27. Pang R, Poon RPT : Angiogenesis and antiangiogenic therapy in hepatocellular carcinoma. Cancer Letters 242 : 151, 2006 https://doi.org/10.1016/j.canlet.2006.01.008
  28. Schmidt M, Lichtner RB : EGF receptor targeting in therapy-resistant human tumors. Drug Resistance Updates 5 : 11, 2002 https://doi.org/10.1016/S1368-7646(02)00004-3
  29. Yao JC : Molecular targeted therapy for carcinoid and islet-cell carcinoma. Best Practice & Research Clinical Endocrinology & Metabolism 21 : 163, 2007 https://doi.org/10.1016/j.beem.2007.01.006
  30. Park YW : Cellular and molecular characterization of adenoid cystic carcinoma of the salivary glands. J Kor Acad Maxillofac Plast Reconst Surg 27(2) : 110, 2005
  31. Park YW, In YS : Immunohistochemical assays for the expression of angiogenic signaling molecules and microvessel density in adenoid cystic carcinomas of human salivary glands. J Kor Assoc Oral Maxillofac Surg 32(6) : 530, 2006
  32. In YS, Kim SM, Park YW : Comparative immunohistochemical assays for the expression of angiogenic factors in tumors of human salivary glands. J Kor Acad Maxillofac Plast Reconst Surg 29(1) : 10, 2007
  33. Jang JH, Kwon KJ, Park YW : Expressions of vascular metastasis related actors in murine orthotopic tumor models of salivary glands. J Kor Acad axillofac Plast Reconst Surg 29(6) : 499, 2007
  34. Beltran D, Faquin WC, Gallagher G et al : Selective immunohistochemical comparison of polymorphous lowgrade adenocarcinoma and adenoid cystic carcinoma. J Oral Maxillofac Surg 64 : 415, 2006 https://doi.org/10.1016/j.joms.2005.11.027
  35. Hartenbach EM, Olson TA, Moganraj GD et al : Vascular endothelial growth factor(VEGF) expression and survival in human epithelial ovarian carcinomas. Cancer Letters 121 : 169, 1997 https://doi.org/10.1016/S0304-3835(97)00350-9
  36. Ribatti D, Cruz A, Nico B et al : in situ hybridization and immunogold localization of vascular endothelial growth factor receptor-2 on the pericytes of the chick chorioallantoic membrane. Elsevier Science Ltd 17(5) : 262, 2002 https://doi.org/10.1006/cyto.2002.1002
  37. Fukuzawa M, Sugiura H, Koshinaga T et al : Expression of vascular endothelial growth factor and its receptor Flk-1 in human neuroblastoma using in situ hybridization. Journal of Pediatric Surgery 37(12) : 1747, 2002 https://doi.org/10.1053/jpsu.2002.36712
  38. Blot E, Decaudin D, Veyradier A et al : Cancer-related thrombotic microangiopathy secondary to von vellibrand factor-cleaving protease dificiency. Thrombosis Research 106 : 127, 2002 https://doi.org/10.1016/S0049-3848(02)00095-6
  39. Morganti M, Mittermayer C, Hanze U et al : Expression of tissue-type plasminogen activator, plasminogen activator inhibitor and von willebrand factor in the supernatant of endothelial cell cultures in response to the seeding of adenocarcinoma cell line HRT-18. Biomed & Pharmacother 50 : 373, 1996 https://doi.org/10.1016/S0753-3322(96)89671-5
  40. Morganti M, Carpi A, Amo-Takyi B et al : Von Villebrand's factor mediates the adherence of human tumoral cells to human endothelial cells and ticlopidine interferes with this effect. Biomed & Pharmacother 54 : 431, 2000 https://doi.org/10.1016/S0753-3322(00)00006-8
  41. Davies DE, Chamberlin SG : Targeting the epidermal growth factor receptor for therapy of carcinomas. Biochemical Pharmacology 51 : 1101, 1996 https://doi.org/10.1016/0006-2952(95)02232-5
  42. Gao ZN, Wei YQ, Yang PS et al : Combined effects of soluble vascular endothelial growth factor receptor FLT-1 gene therapy and cisplantin chemotherapy in human tongue carcinoma xenografts. Oral Oncology 43 : 477, 2007 https://doi.org/10.1016/j.oraloncology.2006.05.009