Enhanced activation of matrix metalloproteinase-9 correlates with the degree of papillary thyroid carcinoma infiltration

Abstract

AimTo determine whether matrix metalloproteinase-9 (MMP-9) may be a useful adjunctive tool for predicting unfavorable biological behavior of papillary thyroid carcinoma (PTC) by evaluating the expression profile and proteolytic activity of MMP-9 in PTC by different techniques and correlating the findings with clinicopathological prognostic factors.MethodsImmunohistochemical localization of MMP-9 was analyzed with antibodies specific for either total or active MMP-9. Activation ratios of MMP-9 were calculated by quantifying gel zymography bands. Enzymatic activity of MMP-9 was localized by in situ zymography after inhibiting MMP-2 activity.ResultsImmunostaining of total and active MMP-9 was observed in tumor tissue and occasionally in non-neoplastic epithelium. Only active MMP-9 was significantly associated with extrathyroid invasion, lymph-node metastasis, and the degree of tumor infiltration (P < 0.001, P = 0.004, and P < 0.001, respectively). Gelatin zymography revealed a correlation between the MMP-9 activation ratio and nodal involvement, extrathyroid invasion, and the degree of tumor infiltration. In situ zymography showed that gelatinases exerted their activity in tumor parenchymal and stromal cells. Moreover, after application of MMP-2 inhibitor, the remaining gelatinase activity, corresponding to MMP-9, was highest in cancers with the most advanced degree of tumor infiltration.ConclusionsThis is the first report suggesting that the evaluation of active MMP-9 by immunohistochemistry and determination of its activation ratio by gelatin zymography may be a useful adjunct to the known clinicopathological factors in predicting tumor behavior. Most important, in situ zimography with an MMP-2 inhibitor for the first time demonstrated a strong impact of MMP-9 activity on the degree of tumor infiltration during PTC progression.

Values of ultrasound features and MMP-9 of papillary thyroid carcinoma in predicting cervical lymph node metastases

“…All these three types of peripheral rings could be found in the PTCs without cervical LNM ( P > 0.05), whereas irregular no-enhancement ring was the most common type in the PTC with cervical LNM ( P < 0.05). The adjacent thyroid tissue could be invaded by cancer, which might cause the appearance of the peripheral irregular no-enhancement ring as a result of the interstitial edema and fibrosis, hyaline degeneration or necrosis 24 , 25 . Peripheral ring was not a common feature of PTC, but the irregular no-enhancement ring may predict the risk of cervical LNM comparing with other three types of peripheral rings ( P = 0.04).…”

“…The staining for active MMP-9 in tumor tissue was graded as follows according to the staining intensity and distribution of immunoreactivity within a single tissue section 25 : (0) no reaction (−); (1) weak reaction (+); (2) moderate reaction (++); (3) intense reaction (+++). Immunohitochemical staining results was evaluated by two independent observers, with high concordance.…”

Knockdown of KDM1A suppresses tumour migration and invasion by epigenetically regulating the TIMP1/MMP9 pathway in papillary thyroid cancer

“…39 MMP9 is a cancer promoter in PTC, for example, MMP9 is up-regulated and correlates with tumour diameter, lymph node metastasis, degree of PTC infiltration and clinical stage. 40,41 We found that si-KDM1A reduced MMP9 expression and activation, suggesting that it may promote tumour progression by regulating MMP9.…”

Chi-Ju-Di-Huang-Wan protects rats against retinal ischemia by downregulating matrix metalloproteinase-9 and inhibiting p38 mitogen-activated protein kinase

“…2.475 mL (Merck KGaA, Darmstadt, Germany); 10 % (w/v) ammonium persulfate 0.1 mL (Sigma-Aldrich, St. Louis, USA); N , N , N’ , N’ tetramethylethylenediamine 0.01 mL (J.T.Baker Inc., Phillipsburg, NJ, USA); Sterile deionised water 4.625 mL)] with 0.1 % gelatin (Sigma-Aldrich, St. Louis, USA) as protease substrate [25]. After separation by electrophoresis, the gel was incubated in renaturation buffer (2.7 % Triton X-100 in distilled water) at room temperature with gentle shaking for 30 min.…”