Evaluation of Matrix Metalloproteinases, Cytokines and Their Potential Role in the Development of Ovarian Cancer

Abstract

BackgroundOvarian cancer is the 5th most common cause of deaths in the women among gynecological tumors. There are many growing evidences that stress and other behavioral factors may affect cancer progression and patient survival. The purpose of this study is to determine the key role of matrix metalloproteinases (MMPs), and cytokines in the aggregation and progression of ovarian cancer.MethodologyStress variables (MDA, AGEs, AOPPs, NO), profile of antioxidants (SOD, Catalase, Vitamin E & A, GSH, GRx, GPx) and inflammatory biomarkers (MMP-9, MMP-2, MMP-11, IL-1α and TNF-α) were biochemically assessed from venous blood of fifty ovarian cancer patients and twenty healthy control subjects. The results of all parameters were analyzed statistically by independent sample t-test.ResultsThe results of the study demonstrated that the levels of stress variables like MDA (3.38±1.12nmol/ml), AGEs (2.72±0.22 ng/ml), AOPPs (128.48±27.23 ng/ml) and NO (58.71±8.67 ng/ml) were increased in the patients of ovarian cancer as compared to control individuals whereas the profile of antioxidants like SOD, Catalase, Vitamin E, Vitamin A, GSH and GRx were decreased in ovarian cancer patients (0.11±0.08 μg/ml, 2.41±1.01μmol/mol of protein, 0.22±0.04 μg/ml, 45.84±9.07μg/ml, 4.88±1.18μg/ml, 5.33±1.26 μmol/ml respectively). But the level of GPx antioxidant was increased in ovarian cancer patients (6.58±0.21μmol/ml). Moreover the levels of MMP-9 (64.87±5.35 ng/ml), MMP-2 (75.87±18.82 ng/ml) and MMP-11 (63.58±8.48 ng/ml) were elevated in the patients. Similarly, the levels of various cytokines TNF-α and IL-1α were also increased in the patients of ovarian cancer (32.17±3.52 pg/ml and 7.04±0.85 pg/ml respectively).ConclusionMMPs are commonly expressed in ovarian cancer which are potential extrapolative biomarkers and have a major role in metastasis. Due to oxidative stress, different cytokines are released by tumor associated macrophages (TAMs) that result in the cancer progression. Consequently, tissue inhibitors of matrix metalloproteinases (TIMPs) are the valuable therapeutic approaches to complement conservative anticancer strategies.

Relationship between matrix metalloproteinases and the occurrence and development of ovarian cancer

“…Evidence has been reported supporting the strong association between other members of the MMPs family and the occurrence, development, and metastasis of ovarian cancer ( 29 ). Qiu et al ( 13 ) found that the regulation of MMP-3 and MMP-2 expression is involved in the estradiol-induced migration and invasion of SKOV3 cells.…”

TGFβ1 in fibroblasts-derived exosomes promotes epithelial-mesenchymal transition of ovarian cancer cells

“…Although the role of TGFβ in ovarian cancer has been studied extensively, the function of TGFβ1 and TGFβ2 in exosomes remains to be explored to understand how these cytokines contribute to EMT in ovarian cancer. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are proteases that are capable of degrading the extracellular matrix to support cancer cell escape from the primary tumor site and metastasis in ovarian cancer [ 23 – 25 ]. Recent studies report that tumor cell-derived exosomes promote an EMT phenotype through MMPs and TGFβ as cargo components [ 26 , 27 ].…”

Association between matrix metalloproteinases polymorphisms and ovarian cancer risk: A meta-analysis and systematic review

“…Matrix metalloproteinases (MMPs), a family of more than 20 zinc-dependent enzymes known to degrade extracellular matrix and basement membrane components [ 7 ], are not only a prerequisite for multiple steps of cancer development but also play important roles in cancer invasion and metastasis [ 8 ]. MMPs are correlated with ovarian cancer, with the levels of MMP-2, MMP-7 and MMP-9 elevated in ovarian cancer patients [ 9 – 10 ]. At genetic level, a number of studies have been carried out to assess the association between polymorphisms of MMPs and ovarian cancer risk [ 11 – 27 ], but the conclusions have been still conflicted and even contradictory.…”