Overexpression of the matrix metalloproteinase 11 gene is a potential biomarker for type 1 endometrial cancer

Abstract

Metalloproteinase matrix 11 (MMP11) is a member of the matrix metalloproteinase family, which are able to degrade extracellular matrix components, and may serve a central function in the enhancement of tumor-induced angiogenesis, cell migration, proliferation, apoptosis and connective tissue degradation. In the present study, gene expression was investigated using the reverse transcription-polymerase chain reaction in 68 cases of type I endometrial carcinoma, and all data were analyzed in association with clinical characteristics. Overexpression of was demonstrated in 75%, and sub-expression was demonstrated in 25%, of endometrial cancer cases. Sub-expression cases were associated with good histological parameters, including low histological grade (G1 and G2), early pathological stage, and absence of vascular invasion, metastasis and recurrence. In total, 76.4% of endometrial cancer cases with sub-expression were identified as early stage 1A and B; however, 23.6% of cases were identified as stage 2, with vascular invasion present in 29.4% of cases. On the other hand, cases which demonstrated overexpression with high ranges (>10 times more than control) were associated with adverse histopathological characteristics, including high grade tumor (G3) and vascular invasion. In conclusion, the increased expression of may be used as a prognostic biomarker in patients with type 1 endometrial cancer.

Changes in the Extracellular Matrix in Endometrial and Cervical Cancer: A Systematic Review

“…They not only contribute to physiological processes but are also responsible for molecular interactions between tumour and stroma [ 23 ]. Higher activity of MMPs has been associated with tumour invasion and metastasis in the course of destruction of extracellular matrix components [ 18 , 21 , 24 , 25 ]. On the other hand, inhibition of MMP activity has been shown to contribute to the reduction in cellular invasion in vitro and the progression of metastasis in vivo [ 26 ].…”

“…Increased expression and activation of MMPs are observed in most cancer tissues compared with normal tissues [ 18 ]. MMPs also contribute to cell proliferation, survival, and angiogenesis [ 21 , 24 ]. Several factors stimulate the synthesis, secretion, and activation of MMPs [ 21 ].…”

“…Physiologically, their expression is controlled by transcription [ 18 ]. MMPs, together with tissue inhibitors of metalloproteinases (TIMPs), play an important role in extracellular matrix transformation [ 24 ]. Tissue inhibitors of metalloproteinases (TIMPs) are inhibitors of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and MMPs.…”

“…Expression of MMP-11 in patients with endometrial cancer type 1 is also associated with poor prognosis. MMP-11 is the only MMP secreted in active form and is unable to degrade the major components of ECM [ 24 ]. It plays an important role in cancer progression and its overexpression could be used as a biomarker in endometrioid-type carcinomas.…”

“…It plays an important role in cancer progression and its overexpression could be used as a biomarker in endometrioid-type carcinomas. Gomez-Macias et al pointed out that elevated MMP-11 levels could be associated with poor prognosis in patients with type I EC [ 24 ]. Skrzypczak et al noted a slight change in MMP-11 expression levels in the G1 cancer subgroup, whereas there was no significant change in expression levels in the other subgroups, which may suggest that MMP-11 has a specific function in the early stages of carcinogenesis [ 30 ].…”