후두암 세포주에서 $TGF-{\beta}1$에 의한 MMP2와 MMP9의 발현 양상

The Effect of Transforming Growth Factor-${\beta}1$ on Expression of MMP 2 and MMP 9 Cell Lines

  • 권남영 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 김형진 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 우정수 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 권순영 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 정광윤 (고려대학교 의과대학 이비인후-두경부외과학교실)
  • Kwon Nam-Young (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Kim Hyung-Jin (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Woo Jeong-Su (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Kwon Soon-Young (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine) ;
  • Jung Kwang-Yoon (Department of Otolaryngology-Head and Neck Surgery, Korea University, College of Medicine)
  • 발행 : 2002.11.01

초록

Backgrounds and Objectives: Metastasis is a complex multistep process that requires sequential interactions between the invasive cell and the extra-cellular matrix. Transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a multifunctional regulator of cellular differentiation, motility and growth. Loss of sensitivity to the growth inhibitory effects by $TGF-{\beta}1$ plays important roles in neoplastic progression. The aim of this study was to investigate the role of $TGF-{\beta}1$ in the neoplastic invasion and metastasis through matrix metalloproteinase (MMP) of laryngeal cancer cell lines. Material and Methods: Two laryngeal cancer cell lines, SNU-899 and SNU-1076 were treated with recombinant $TGF-{\beta}1$, and the expression of MMP-2 and MMP-9 was immunohistochemically evaluated and gelatinase activity was studied by gelatin zymogram. Results: The cell growth inhibition was evident on 4th days after 1ng/ml and 10ng/ml $TGF-{\beta}1$ treatment. The expressions of MMP-2 and MMP-9, and their gelatinase activities were increased in dose-dependent manner. Conclusion: $TGF-{\beta}1$ treatment in laryngeal cancer cell lines induces the expression of MMP-2 and MMP-9, thus playing a role in the digestion of extracellular matrix gelatin.

키워드

참고문헌

  1. Blobe GC, Shiemann WP, Lodish HF : Role of transforming growth factor $\beta$ in human disease. N Engl J Med 2000 ; 342 : 1350-1358 https://doi.org/10.1056/NEJM200005043421807
  2. De Caestecke MP, Roberts P : Role of Transforming Growth Factor-$\beta$ signaling in cancer. J Nat Cancer Inst 2000 ; 92 : 1338-1402
  3. Lee BI, Park SH, Kim JH : MS-275, a histone deacetylase inhibitor selectively induces transforming growth factor $\beta$ type Ⅱ receptor exression in human breast cancer cells. Cancer Res 2001 ; 61 ; 931-934
  4. Malkowitz S, Wang J, Myeroff L : Inactivation of the type Ⅱ TGF-$\beta$ receptor in colon cancer cells with microsatellite instability. Science 1995 ; 268 ; 1336-1338
  5. Massague J : TGF-$\beta$ signal transduction. Annu Rev Biochem 1998 ; 67 : 753-791 https://doi.org/10.1146/annurev.biochem.67.1.753
  6. Pashe B : Role of Transforming Growth Factor $\beta$ in cancer. J Cell Phys 2001 ; 186 : 153-168 https://doi.org/10.1002/1097-4652(200002)186:2<153::AID-JCP1016>3.0.CO;2-J
  7. Takaku K, Oshima M, Miyoshi H : Intestinal tumorigenesis in compound mutant mice of both Smad4 and APC genes. Cell 1998 ; 92 : 645-656 https://doi.org/10.1016/S0092-8674(00)81132-0
  8. Tang B, Bottinger EP, Jakowlew S : Transforming growth factor $\beta$1 is a new form of tumor suppressor with haploid insufficiency. Nat Med 1998 ; 4 : 802-807 https://doi.org/10.1038/nm0798-802
  9. Wrana JL, Attisano L, Wieser R, Ventura F : Mechanism of activation of TGF-$\beta$ receptor, Nature 1994 ; 370 : 341-347
  10. Herron GS, Werb Z, Dwyer K, Banda MJ : Secretion of metallo-proteinases by stimulated capiilary endothelial cells. 1 : Production of procollagenase and prostromelysin exceeds expression of proteolytic activity. J Biol Chem 1986 ; 261 : 2810-2813
  11. Adler RR, Brenner CA : Expression of extracellular matrix-degrading metalloproteinases and metalloproteinases inhibitors is developmentally regulated during endoderm differentiation of embryonal carcinoma cells. Development 1990 ; 110 : 221-220
  12. Kleiner DE, Stetler-Stevenson WG : Quantitative zymography : detection of picogram quantities of gelatinase. Anal Biochem 1994 ; 218 : 325-329 https://doi.org/10.1006/abio.1994.1186
  13. Stetler-Stevenson WG : Progelatinase A activation during tumor cell invasion. Invasion Metastasis 1994 ; 14 : 41-48
  14. Stetler-Stevenson WG, Hewitt R, Corcoran M : Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic. Sem in Cancer Biol 1996 ; 7 : 147-154 https://doi.org/10.1006/scbi.1996.0020
  15. Garbett EA, Reed MWT, Brown NJ : Proteolysis in human cancer. Br J Cancer 1999 ; 81 : 287-293 https://doi.org/10.1038/sj.bjc.6690689
  16. Davies B, Miles DW, Balkwill FR : Activity of type IV collagenases in benign and malignant breast disease. Br J Cancer 1993 ; 67 : 1126-1131 https://doi.org/10.1038/bjc.1993.207
  17. DiLorenzo TP, Steinberg BM : Laryngeal keratinocytes show variable inhibition of replication by TGF-beta. J Cell Sci 1990 ; 96 : 115-119
  18. Hagedorn H, Nerlich A : Expression of TGF-beta 1 protein and mRNA and the effect on the tissue remodeling in laryngeal carcinomas. Anticancer Res 1999 ; 19 : 4265-4272
  19. Sarioglu S, Pabuccuoglu U : Matrix metalloproteinase-2 expression in laryngeal preneoplastic and neoplastic lesions. Pathol Res Pract 2001 ; 197 : 483-486 https://doi.org/10.1078/0344-0338-00115
  20. Ranuncolo SM, Matos E : Circulating 92kDa matrix metallo-proteinase (MMP 9) activity is enhanced in the euglobulin plasma fractior head and neck squamous cell carcinoma. Cancer 2002 ; 94 : 1483-1491 https://doi.org/10.1002/cncr.10356