Maxillofacial Plastic and Reconstructive Surgery

Korean Association of Maxillofacial Plastic and Reconstructive Surgeons (대한악안면성형재건외과학회)
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EXPRESSIONS OF VASCULAR METASTASIS RELATED FACTORS IN MURINE ORTHOTOPIC TUMOR MODELS OF SALIVARY GLANDS

마우스에서 확립된 타액선 동위종양에서 혈관성 전이관련 인자의 발현

  • Jang, Jae-Hyun (Department of Oral and Maxillofacial Surgery, College of Dentistry, Kangnung National University) ;
  • Kwon, Kwang-Jun (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)
  • 장재현 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 권광준 (강릉대학교 치과대학 구강악안면외과학교실) ;
  • 박영욱 (강릉대학교 치과대학 구강악안면외과학교실)
  • Published : 2007.11.30
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Abstract

Background and Purpose: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. Experimental Design: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2. Results: Transplantation of human ACC tumor cell $(5{\times}10^5)$ into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P<0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC. Conclusion: VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

Keywords

References

  1. Chen CH, Li BY, Wan JT et al : Expression of epidermal growth factor in salivary adenoid cystic carcinoma. Proc Natl Sci Counc Repub China B 25(2) : 90, 2001
  2. Hichman RE, Cawson RH, Duffy SW : The prognosis of specific types of salivary gland tumors. Cancer 54 : 1620, 1984 https://doi.org/10.1002/1097-0142(19841015)54:8<1620::AID-CNCR2820540824>3.0.CO;2-I
  3. de Jong JS : Expression of growth factors, growth-inhibiting factors, and their receptors in invasive breast cancer. II: Correlations with proliferation and angiogenesis. J Pathol 184 : 53, 1998 https://doi.org/10.1002/(SICI)1096-9896(199801)184:1<53::AID-PATH6>3.0.CO;2-7
  4. Neuchrist C, Quint C, Pammer A et al : Vascular endothelial growth factor (VEGF) and microvessel density in squamous cell carcinomas of the larynx: an immunohistochemical study. Acta Otolaryngol 119 : 732, 1999 https://doi.org/10.1080/00016489950180711
  5. Obermair A. Kohlberger P, Bancher-Todesca D et al : Influence of microvessel density and vascular permeability factor/ vascular endothelial growth factor expression on prognosis in vulvar cancer. Gynecol Oncol 63 : 204, 1996 https://doi.org/10.1006/gyno.1996.0307
  6. Goldman CK : Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. Mol Biol Cell 4 : 121. 1993
  7. Fidler IJ : Rationale and methods for the use of nude mice to study the biology and therapy of human cancer metastasis. Cancer Metastasis Rev 5: 29, 1986 https://doi.org/10.1007/BF00049529
  8. Bowden J, Brennan PA. Umar T et al : Expression of vascular endothelial growth factor in basal cell carcinoma and cutaneous squamous cell carcinoma of the head and neck. J Cutan Pathol 29 : 585, 2002 https://doi.org/10.1034/j.1600-0560.2002.291003.x
  9. Gille J, Swerlick RA, Caughman SW : Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation. Embo J 16 : 750, 1997 https://doi.org/10.1093/emboj/16.4.750
  10. Yu F, Jiang XZ, Chen WT et al : Microvessel density and expression of vascular endothelial growth factor in adenoid cystic carcinoma of salivary gland. Shanghai Kou Qiang Yi Xue 12 : 443, 2003
  11. Luca M, Huang S, Gershenwald JE et al : Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol 151 : 41. 1997
  12. Bergers G, Brekken R. McMahon G et al : Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2 : 737, 2000 https://doi.org/10.1038/35036374
  13. Myoken Y, Myoken Y, Okamoto T et al : Immunohistochemical study of overexpression of fibroblast growth factor-1 (FGF-1), FGF-2, and FGF receptor-1 in human malignant salivary gland tumours. J Pathol 178 (4): 429, 1996 https://doi.org/10.1002/(SICI)1096-9896(199604)178:4<429::AID-PATH495>3.0.CO;2-1
  14. Koch AE, Polverini PJ, Kunkel SL et al : Interleukin-8 as a macrophage derived mediator of angiogenesis. Science 258 : 1798, 1992 https://doi.org/10.1126/science.1281554
  15. Ishibashi H. Shiratuchi T, Nakagawa K et al : Hypoxia-induced 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
  16. Park YW, Chung SH : An experimental study for establishment of orthotopic salivary tumor models in mice. J Kor Oral Maxillofac Surg 33(2) : 81. 2007
  17. Park YW : Cellular and molecular characterization of adenoid cyctic carcinoma of the salivary glands. J Kor Assoc Of Maxillofac Plast And Reconstr Surg 27 : 110, 2005
  18. 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 : 530. 2006
  19. In YS, Kim SM, Park YW: Comparative immunohistochemical assays for the expression of angiogenic factors in tumors of human salivary glands. J Kor Assoc Maxillofac Plast Reconstr Surg 29 : 10, 2007
  20. Park YW, Chung SH : An experimental study for establishment of orthotopic salivary tumor models in mice. J Kor Assoc Oral Maxillofac Surg 33 : 81. 2007
  21. Fidler IJ. Ellis LM : The implications of angiogenesis for the biology and therapy of cancer metastasis. Cell 79 : 185, 1994 https://doi.org/10.1016/0092-8674(94)90187-2
  22. Arenberg DA, Keane MP. DiGiovine B et al : Epithelial-neutrophil activating peptide is an important angiogenic factor in non-small cell, lung cancer. J Clin Invest 102 : 465, 1988 https://doi.org/10.1172/JCI3145
  23. Brew R, Southern SA, Flanagan BF et al : Detection of interleukin-8 mRNA and protein in human colorectal carcinoma cells. Eur J Cancer 32 : 2142. 1996 https://doi.org/10.1016/S0959-8049(96)00221-3
  24. Green GF. Kitadai Y, Pettaway CA et al : Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells Implanted in nude mice using an in situ messenger RNA hybridization technique. Am J Pathol 150 : 1571. 1997
  25. Singh R, Gutman M, Reich R et al : UVB irradiation promotes tumorigenic and metastatic properties in primary cutaneous melanoma via induction of IL-8. Cancer Res 54 : 3242, 1995
  26. Yoneda J. Kuniyasu H, Crispen MA et al : Expression of angiogenesis-related genes and progression of human ovarian carcinomas in nude. J Natl Cancer Inst 90 : 447. 1998 https://doi.org/10.1093/jnci/90.6.447
  27. Ferrer FA, Miller LJ, Andrawis RI et al : Angiogenesis and prostate cancer: In vivo and in vitro expression of angiogenesis factors by cancer cells. Urology 51 : 161. 1998
  28. Kitadai Y. Haruma K, Sumii K et al : Expressoin of interleukin-8 correlates with vascularity in human gastric carcinomas. Am J Pathol 152 : 93. 1998
  29. Liotta LA, Steeg PS, Stetler-Stevenson WG : Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64 : 327, 1991 https://doi.org/10.1016/0092-8674(91)90642-C
  30. Aznavoorian S, Murphy AN, Stetler-Stevenson WG et al : Molecular aspects of tumor cell invasion and metastasis. Cancer 71 : 1368, 1993 https://doi.org/10.1002/1097-0142(19930215)71:4<1368::AID-CNCR2820710432>3.0.CO;2-L
  31. Folkman J : Angiogenesis in cencer, vascualr, rheumatoid, and other disease. Nature Med 1 : 27, 1995 https://doi.org/10.1038/nm0195-27
  32. Fong TA, Shawver LK, SUN L, et al. : SU54116 is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR)that inhibits tyrosine kinase catalysis, tumor vascularization, and growth of multiple tumor types. Cancer Res 59 : 99. 1999
  33. Prewett M, Huber J, Li Y et al. : Antivascular endothelial growth factor receptor (fetal liver kinase 1)monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 59 : 5209. 1999
  34. Shaheen RM, Davis DW. Liu W et al. : Antiangiogenic therapy targeting the tyrosine kinase receptor for vascular endothelial growth factor receptor inhibits the growth of colon cancer liver metastasis and induces tumor and endothelial cell apoptosis. Cancer Res 59 : 5412, 1999