Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2014.55.128
Enhanced activation of matrix metalloproteinase-9 correlates with the degree of papillary thyroid carcinoma infiltration
Ilona Marečko
; Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Zemun-Belgrade, Serbia
Dubravka Cvejić
; Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Zemun-Belgrade, Serbia
Sonja Šelemetjev
; Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Zemun-Belgrade, Serbia
Svetlana Paskaš
; Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Zemun-Belgrade, Serbia
Svetislav Tatić
; Institute of Pathology, Medical Faculty, University of Belgrade Belgrade, Serbia
Ivan Paunović
; Center for Endocrine Surgery Institute of Endocrinology, Diabetes and Diseases of Metabolism, Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia
Svetlana Savin
; Institute for the Application of Nuclear Energy – INEP, University of Belgrade, Zemun-Belgrade, Serbia
Sažetak
Aim To 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.
Methods Immunohistochemical 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.
Results Immunostaining 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.
Conclusions This 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.
Ključne riječi
Hrčak ID:
127306
URI
Datum izdavanja:
15.4.2014.
Posjeta: 992 *