Abstract
The sera of 40 patients with gastric cancer and 11 patients as the control group were studied for the detection of matrix metalloproteinases. The malignant behavior of tumor cells mainly depends on the capability of invasion and the metastasis of cancer cells. After the components of the extracellular matrix (ECM) are degraded, tumor cells invade the surrounding tissue and the vascular or lymphatic vessels to form metastasis colonies at distant sites. Extracellular proteolytic enzymes implicate the invasion and metastasis of cancer. Proteolytic enzymes from tumors lead to the breakdown of basement membranes and the ECM, thereby, facilitating cancer cell invasion into the surrounding normal tissue. Proteinase activity is overexpressed in the serum of stage 3 and 4 tumors compared to stage 1 and 2 tumors. ProMMP-9 was detected in the serum of patients of gastric cancer by SDS polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-PAGE zymography, with its molecular mass of 92 kDa. MMP-9 in serum plays an important role in the progression of gastric cancer.
Similar content being viewed by others
References
Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S. Reduced angiogenesis and tumor progression in gelatinase A––deficient mice. Cancer Res. 1998;58:1048–1051.
Liotta LA. Tumor invasion and metastases: role of the extracellular matrix: Rhoads memorial award lecture. Cancer Res. 1986;46:1–7. doi:10.1016/S0065-230X(08)60034-2.
Liotta LA, Tryggvason K, Garbis S, Hart I, Foltz CM, Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980;284:67–68. doi:10.1038/284067a0.
Mc Cawley LJ, Matrisian LM. Matrix metalloproteinases: multifunctional contributors to tumor progression. Mol Med Today. 2000;6(4):149–156. doi:10.1016/S1357-4310(00)01686-5.
Zucker S, Lysik RM, Zarrabi MH, Moll U. M(r) 92,000 type IV collagenase is increased in plasma of patients with colon cancer and breast cancer. Cancer Res. 1993;53:140–146.
Hoikkala S, Paakko P, Soini Y, Makitaro R, Kinnula V, Turpeenniemi-Hujanen T. Tissue MMP-2/TIMP-2-complex are better prognostic factors than serum MMP-2, MMP-9 or TIMP-1 in stage I-III lung carcinoma. Cancer Lett. 2005;236:125–132. doi:10.1016/j.canlet.2005.05.012.
Ruokolainen H, Paakko P, Turpeenniemi-Hujanen T. Serum matrix metalloproteinase-9 in head and neck squamous cell carcinoma is a prognostic marker. Int J Cancer. 2005;116:422–427. doi:10.1002/ijc.21092.
Shen KH, Chi CW, Lo SS, Kao HL, Lui WY, Wu CW. Serum matrix metalloproteinase-9 level associated with stromal reaction in patients with gastric cancer. Anticancer Res. 2000;20:1307–1310.
Hayasaka A, Suzuki N, Fujimoto N, et al. Elevated plasma levels of matrix metalloproteinase-9 (92 kDa type IV collagenase/gelatinase B) in hepatocellular carcinoma. Hepatology. 1996;24:1058–1062. doi:10.1002/hep.510240513.
Endo K, Maehara Y, Baba H, et al. Elevated levels of serum and plasma metalloproteinases in patient with gastric cancer. Anticancer Res. 1997;17:2253–2255.
Torii A, Kodera Y, Uesaka K, et al. Plasma concentration of matrix metalloproteinase 9 in gastric cancer. Br J Surg. 1997;84:133–136. doi:10.1002/bjs.1800840147.
Souza-Tarla CD, Uzuelli JA, Machado AA, Gerlach RF, Tanus-Santos JE. Methodological issues affecting the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activites. Clin Biochem. 2005;38(5):410–414. doi:10.1016/j.clinbiochem.2005.02.010.
Gerlach RF, Uzuelli JA, Souza-Tarla CD, Tanus-Santos JE. Effect of anticoagulants on the determination of plasma matrix metalloproteinase (MMP)-2 and MMP-9 activites. Anal Biochem. 2005;344(1):147–149. doi:10.1016/j.ab.2005.04.038.
Gerlach RF, Demacq C, Jung K, Tanus-Santos JE. Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma. Clin Biochem. 2007;40(1–2):119–123. doi:10.1016/j.clinbiochem.2006.10.007.
Manello F, Tanus-Santos JE, Meschiari CA, Tonti GA. Differences in both matrix metalloproteinase 9 concentration and zymographic profile between plasma and serum with clot activators are due to the presence of amorphous silica or silicate salts in blood collection devices. Anal Biochem. 2008;374:56–63. doi:10.1016/j.ab.2007.11.020.
Ebeling W, Hennrich N, Klockow M, Metz H, Orth HD, Lang H. Protenase K from Tritirachium album. Eur J Biochem. 1974;47:91–97. doi:10.1111/j.1432-1033.1974.tb03671.x.
Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–685. doi:10.1038/227680a0.
Kleiner DE, Stetler-Stevenson WG. Quantative zymography detection of picogram quantities of gelatinases. Anal Biochem. 1994;218:325–329. doi:10.1006/abio.1994.1186.
Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the Biuret reaction. J Biol Chem. 1949;177:751–766.
Aznovoorian S, Murphy AN, Stettler-Stevenson WG, Liotta LA. Molecular aspects of tumor cells invasion and metastasis. Cancer. 1993;71:1368–1383. doi :10.1002/1097-0142(19930215)71:4<1368::AID-CNCR2820710432>3.0.CO;2-L.
Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem. 1999;274:21491–21494. doi:10.1074/jbc.274.31.21491.
Westermarck J, Kahari VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 1999;13:781–792.
Ellenrieder V, Adler G, Gress TM. Invasion and metastasis in pancreatic cancer. Ann Oncol. 1999;10S:45–50.
Kallakury BV, Karikehalli S, Haholu A, Sheehan CE, Azumi N, Ross JS. Increased expression of matrix metalloproteinases 2 and tissue inhibitors of metalloproteinases 1 and 2 correlate with poor prognostic variables in renal cell carcinoma. Clin Cancer Res. 2001;7:3113–31199.
Sier CF, Kubben FJ, Ganesh S, et al. Tissue levels of matrix metalloproteinases MMP-2 and MMP 9 are related to the overall survival of patients with gastric carcinoma. Br J Cancer. 1996;74:413–417.
Kabashima A, Maehara Y, Kakeji Y, Baba H, Koga T, Sugimachi K. Clinicopathological features and overexpression of matrix metalloproteinases in intramucosal gastric carcinoma with lymph node metastasis. Clin Cancer Res. 2000;6:3581–3584.
Paez Preda M, Ledda MF, Goldberg V, et al. High levels of matrix metalloproteinases regulate proliferation and hormone secretion in pituitary cells. J Clin Endocrinol Metab. 2000;85:263. doi:10.1210/jc.85.1.263.
Kubben FJGM, Sier CFM, van Duijn W, et al. Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer. Br J Cancer. 2006;94:1035–1040. doi:10.1038/sj.bjc.6603041.
Wu CY, Wu MS, Chiang EP, et al. Plasma matrix metalloproteinase-9 level is better than serum matrix metalloproteinase-9 level to predict gastric cancer evolution. Clin Cancer Res. 2007;13(7):2054–2060. doi:10.1158/1078-0432.CCR-06-2299.
Kattan MW. Judging new markers by their ability to improve predictive accuracy. J Natl Cancer Inst. 2003;95:634–635.
Kattan MW, Karpeh MS, Mazymdar M, Brennan MF. Postoperative nonogram for disease-specific survival after an RO resection for gastric cancer carcinoma. J Clin Oncol. 2003;21:3647–3650. doi:10.1200/JCO.2003.01.240.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dragutinović, V., Izrael-Živković, L. & Radovanović, N. Relation of Matrix Metalloproteinase-9 to Different Stages of Tumors in the Serum of Gastric Cancer. Dig Dis Sci 54, 1203–1207 (2009). https://doi.org/10.1007/s10620-008-0472-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-008-0472-y