MMP-10, MMP-7, TIMP-1 and TIMP-2 mRNA expression in esophageal cancer

  • Agnieszka Juchniewicz Department of Clinical Molecular Biology, Medical University of Bialystok, 13 Waszyngtona Str, 15-267, Bialystok, Poland
  • Oksana Kowalczuk Department of Clinical Molecular Biology, Medical University of Bialystok, 13 Waszyngtona Str, 15-267, Bialystok, Poland
  • Robert Milewski Department of Statistic and Medical Informatics, Medical University of Bialystok, 37 Szpitalna Str, 15-295 Bialystok, Poland
  • Wojciech Laudański Department of Thoracic Surgery, Medical University of Bialystok, 24A M. Skłodowskiej-Curie Str, 15-267, Bialystok, Poland
  • Piotr Dzięgielewski Department of Thoracic Surgery, Medical University of Bialystok, 24A M. Skłodowskiej-Curie Str, 15-267, Bialystok, Poland
  • Mirosław Kozłowski Department of Thoracic Surgery, Medical University of Bialystok, 24A M. Skłodowskiej-Curie Str, 15-267, Bialystok, Poland
  • Jacek Nikliński Department of Clinical Molecular Biology, Medical University of Bialystok, 15-267 Białystok, Poland.
Keywords: Esophageal cancer, gene expression, metalloproteinases,

Abstract

Introduction: Tissue inhibitors of metalloproteinases (TIMP) and the matrix metalloproteinases (MMP) are involved in the spread of cancer. Methods: We have evaluated the matrix metalloproteinases’ (MMP-10, MMP-7) and their inhibitors’ (tissue inhibitors of metalloproteinases – TIMP-1, TIMP-2) mRNA expression in 61 esophageal cancer samples from patients who had undergone surgery, by using real-time quantitative RT-PCR, and correlated the results with the patient clinicopathologic features. Results: MMP-10, MMP-7, TIMP-1, TIMP-2 were overexpressed in 73%, 85%, 55% and 42% of esophageal cancer samples, respectively. The expression of MMP-10, TIMP-1, and TIMP-2 correlated with the tumor size. The MMP-7 overexpression was associated with the tumour stage (I, II vs III, p=0.05) and lymph node metastasis (N0 vs N1, p=0.037). Conclusions: We conclude that in the resected esophageal cancer an increased mRNA expression of MMP-7, MMP-10 and TIMP-1 correlated with clinicopathologic features. We suggest that these genes may play a role during progression of the disease.

References

Alakus H, Grass G, Hennecken J, et al. (2008) Clinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer. Histol Histopathol. 23: 917–923.

Baker AH, Edwards DR, Murphy G. (2002) Metalloproteinase inhibitors: biological actions and therapeutic opportunities. J Cell Sci. 115(19):3719-3727. DOI:10.1242/jcs.00063

Bollschweiler E, Hölscher AH (2007) Prognosis of Early Esophageal Cancer: Differences Between Squamous Cell Carcinoma and Adenocarcinoma. Ann Surg. 245(2): 334 DOI:10.1097/01.sla.0000253072.33351.a4

Borchers AH, Powell MB, Fusenig NE, Bowden GT. (1994) Paracrine factor and cell-cell contact-mediated induction of protease and c-ets gene expression in malignant keratinocyte/dermal fibroblast cocultures. Exp Cell Res. 213(1): 143-147 DOI:10.1006/excr.1994.1183

Deryugina EI, Quigley JP. (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev. 25(1): 9-34 DOI:10.1007/s10555-006-7886-9

Edge SB, ByrD DR, Compton CC, Fritz AG, Greene FL, Trotti A. (2010) Esophagus and esophagogastric junction. In: Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, ed. AJCC cancer staging manual. 7th ed. New York: Springer,103-107

Gu ZD, Li JY, Li M, et al. (2005) Matrix metalloproteinases expression correlates with survival in patients with esophageal squamous cell carcinoma. Am J Gastroenterol. 100(8):1835-1843 DOI:10.1111/j.1572-0241.2005.50018.x

Jian GY, Goldberg ID, Shi YE. (2002) Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene. 21(14):2245-2252 DOI:10.1038/sj.onc.1205291

Juchniewicz A, Niklińska W, Kowalczuk O, et. al, (2015) Prognostic value of vascular endothelial growth factor-C and podoplanin mRNA expression in esophageal cancer. Oncol Lett. 10(6): 3668-3674 DOI: 10.3892/ol.2015.3824

Kähäri VM, Saarialho-Kere U. (1999) Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med. 31:34–45.

Kollarova H, Machova L, Horakova D, Janoutova G, Janout V. (2007) Epidemiology of esophageal cancer - an overview article. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 151(1): 17-20.

Kozłowski M, Laudański W, Mroczko B, Szmitkowski M, Milewski R, Łapuć G, (2013) Serum tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A) are associated with prognosis in esophageal cancer patients. Adv Med Sci. 58(2): 227-234 DOI:10.2478/ams-2013-0017

Leeman MF, Curran S, Murray GI. (2003) New insights into the roles of matrix metalloproteinases in colorectal cancer development and progression. J Pathol. 201(4): 528-534 DOI:10.1002/path.1466

Lozano R, Naghavi M, Foreman K, et al. (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 380(9859): 2095-2128. DOI: 10.1016/S0140-6736(12)61728-0.

Lynch CC, Matrisian LM. (2002) Matrix metalloproteinases in tumor-host cell communication. Differentiation. 70(9-10): 561-573 DOI:10.1046/j.1432-0436.2002.700909.x

Mimori K, Mori M, Shiraishi T, et. al. (1997) Clinical significance of tissue inhibitor of metalloproteinase expression in gastric carcinoma. Br J Cancer. 76(4): 531-536.

Miyata Y, Iwata T, Ohba K, et al. (2006) Expression of matrix metalloproteinase-7 on cancer cells and tissue endothelial cells in renal cell carcinoma: prognostic implications and clinical significance for invasion and metastasis. Clin Cancer Res. 12(23): 6998-7003 DOI:10.1158/1078-0432.CCR-06-1626

Mori M, Mimori K, Sadanaga N, et al. (2000) Prognostic impact of tissue inhibitor of matrix metalloproteinase-1 in esophageal carcinoma. Int J Cancer. 88(4): 575-578. DOI:10.1002/1097-0215(20001115)88:4<575::AID-IJC9>3.0.CO;2-C

Mroczko B, Groblewska M, Łukaszewicz-Zajac M, Bandurski R, Kedra B, Szmitkowski M. (2009) Pre-treatment serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in gastric cancer patients. Clin Chem Lab Med. 47(9):1133-1139 DOI:10.1515/CCLM.2009.253

Mroczko B, Łukaszewicz-Zając M, Wereszczyńska-Siemiątkowska U, et al. (2009) Clinical significance of the measurements of serum matrix metalloproteinase-9 and its inhibitor (tissue inhibitor of metalloproteinase-1) in patients with pancreatic cancer: metalloproteinase-9 as an independent prognostic factor. Pancreas. 38(6): 613-618 DOI:10.1097/MPA.0b013e3181a488a0.

Mukherjee S, Roth MJ, Dawsey SM, et al. (2010) Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma. J Transl Med. 8: 91. DOI:10.1186/1479-5876-8-91.

Nabeshima K, Inoue T, Shimao Y, Sameshima T. (2002) Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int. 52:255–264 DOI:10.1046/j.1440-1827.2002.01343.x

Rydlova M, Holubec LJR, Ludvikova MJR, et al. (2008) Biological activity and clinical implications of the matrix metalloproteinases. Anticancer Res; 28(2B): 1389-1397.

Salmela MT, Karjalainen-Lindsberg ML, Puolakkainen P, Saarialho-Kere U. (2001) Upregulation and differential expression of matrilysin (MMP-7) and metalloelastase (MMP-12) and their inhibitors TIMP-1 and TIMP-3 in Barrett's esophageal adenocarcinoma. Br J Cancer. 85(3): 383-392. DOI:10.1054/bjoc.2001.1929

Samantaray S, Sharma R, Chattopadhyaya TK, Gupta SD, Ralhan R. (2004) Increased expression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol. 130(1):37-44. DOI:10.1007/s00432-003-0500-4

Sato H, Kida Y, Mai M, Endo Y, Sasaki T. (1992) Expression of genes encoding type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells. Oncogene. 7(1): 77-83.

Schmittgen TD, Livak KJ (2008): Analyzing real‑time PCR data by the comparative C(T) method. Nat Protoc 3: 1101-1108,

Sharma R, Chattopadhyay TK, Mathur M, Ralhan R. (2004) Prognostic significance of stromelysin-3 and tissue inhibitor of matrix metalloproteinase-2 in esophageal cancer. Oncology. 67(3-4): 300-309 DOI:10.1159/000081331

Stetler-Stevenson WG. (2001) The role of matrix metalloproteinases in tumor invasion, metastasis, and angiogenesis. Surg Oncol Clin N Am. 10(2):383-392.

Szarvas T, Becker M, Vom Dorp F, et al. (2010) Matrix metalloproteinase-7 as a marker of metastasis and predictor of poor survival in bladder cancer. Cancer Sci. 101(5):1300-1308 DOI:10.1111/j.1349-7006.2010.01506.x

Tanioka Y, Yoshida T, Yagawa T, et al. (2003) Matrix metalloproteinase-7 and matrix metalloproteinase-9 are associated with unfavourable prognosis in superficial oesophageal cancer. Br J Cancer. 89(11): 2116-2121. DOI:10.1038/sj.bjc.6601372

Vallböhmer D, Brabender J, Metzger R, Hölscher AH. (2010) Genetics in the pathogenesis of esophageal cancer: possible predictive and prognostic factors. J Gastrointest Surg. 14: 75-80. DOI:10.1007/s11605-009-1021-5

Visse R, Nagase H. (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 92(8): 827-839 DOI:10.1161/01.RES.0000070112.80711.3D

Yamamoto H, Adachi Y, Itoh F, et al. (1999) Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer Res. 59(14): 3313-3316.

Yamashita K, Mori M, Shiraishi T, Shibuta K, Sugimachi K. (2000) Clinical significance of matrix metalloproteinase-7 expression in esophageal carcinoma. Clin Cancer Res. 6(3): 1169-1174.

Zhang J, Jin X, Fang S, et al. (2005) The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell

Published
2017-07-11
Section
Articles