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Scientists Reveal Connections of Matrix Metalloproteinase Expressions to Ovarian Cancer Prognosis

Sep 23, 2019

A study team with Hefei Institutes of Physical Science conducted a study in matrix metalloproteinase in ovarian cancer to find their connections behind, which may shed new light on ovarian cancer treatment.

Ovarian cancer is one kind of highly lethal cancer and even is often not detected until late stages. Previous studies have found that high expressions of MMPs correlates cancer invasion, metastasis, and poor prognosis.

However, there studies do exist to indicate MMPs, in certain situations, might inhibit cancer rather than promoting it. Thus, what is the role of different MMPs in different cancer types needs to be further explored.

In this work, the team used RNA-Seq and corresponding clinical data from TCGA to analyze the correlations between MMP expressions and the clinicopathologic characteristics and outcome in ovarian serous cystadenocarcinoma (OSC) patients.

The team found MMP-3 was significantly increased in high-grade and high-stage tumors compared with low-grade and low-stage ones.

Using univariate analysis and multivariate Cox model, high expressions of MMP-19 and -20 were found to associate with poor overall survival independent of clinicopathologic characteristics.

Moreover, using in vitro studies, ovarian cancer cell lines with higher MMP-19 and -20 protein expressing levels were associated with anti-cancer drugs resistance, while knockdown of MMP-19 or -20 increased ovarian cancer cell sensitivities to several clinical using chemotherapy agents.

The study also uncovered that knockdown of MMP-19 or -20 degrade the invasion abilities of several ovarian cancer cell lines.

The team believed their in vitro studies revealed potential mechanisms of high MMP-19 and -20 expressions in the poor prognosis of ovarian cancer.

This study was supported by grant from the National Natural Science Foundation of China, and the One Hundred Talents Projects of the Chinese Academy of Sciences to Haiming Dai and Jinfu Nie.

 

Figure. MMP-19 and MMP-20 knockdown decreased the invasion abilities of ovarian cancer cells. The normalized percentages of invaded Cov362 (a) and Skov3 (b) afer transfected with MMP-19 siRNA or MMP-20 siRNA or control were indicated as detected by Boyden Chamber Transwell method. (c) A representative cell invasion assay was shown. Cells were transfected with MMP-19 or MMP-20 siRNA or control and incubated for 24 h, seeded into Matrigel-coated transwell inserts, and incubated for another 48 h. Error bars, mean ± S.D. of three independent experiments. *p < 0.05; **p< 0.01; ***p<0.001 (Image by WANG Shujie)

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ZHOU Shu

Hefei Institutes of Physical Science

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Matrix Metalloproteinase Expressions Play Important role in Prediction of Ovarian Cancer Outcome

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