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

Zhang, Y.; Chen, Q.

doi:10.1590/1414-431x20176104

Cited by 42 publications

(47 citation statements)

References 39 publications

(42 reference statements)

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“…Thus, it is critical to understand the contribution of genetic and environmental interactions in the development of ovarian cancer. In this occurrence, TIMPs are natural inhibitors of the MMPs, which are proteolytic enzymes involved in degradation of extracellular matrix, thereby favouring tumour cell invasion and metastasis …”

Section: Discussionmentioning

confidence: 99%

“…In this occurrence, TIMPs are natural inhibitors of the MMPs, which are proteolytic enzymes involved in degradation of extracellular matrix, thereby favouring tumour cell invasion and metastasis. [17][18][19] It has been well established that Tregs contribute to inhibition of the anti-tumour immune response. 20 The efficacy of many immunotherapeutic approaches that target T cell co-inhibitory and co-stimulatory receptors correlate with an altered balance in the ratio of effector T cells to Tregs in favour of the effector cells.…”

Section: Discussionmentioning

confidence: 99%

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Targeting cytokines secreted by CD4⁺CD25^highCD127^low regulatory T cells inhibits ovarian cancer progression

Xing

Shen

2018

Scand J Immunol

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Epithelial ovarian cancer (EOC) is one of the major malignant cancers with high rates of early metastasis in which regulatory T cells (Tregs) play an important role. Tregs suppress immune responses and promote the development of tumours in patients with EOC. However, the underlying mechanisms remain unclear. In this study, we found higher levels of CD4+CD25highCD127low Tregs in patients with EOC than in patients with benign ovarian tumours and healthy donors. The immune inhibitory effect of Tregs functions by maintaining high levels of immunosuppressive cytokines in EOC. The high levels of Tregs and related cytokines (TGF‐β1 or IL‐10) were associated with lymphatic metastasis and FIGO stages of patients with EOC. Expression of matrix metalloproteinase (MMP)‐2 and tissue inhibitors of metalloproteinase (TIMP)‐2 in EOC cell lines were significantly regulated in the coculture experiment with CD4+CD25highCD127low Tregs sorted from EOC patients. Levels of MMP‐2 and TIMP‐2 conversely changed after blocking IL‐10R and TGF‐β1R in EOC cells. The invasion ability of EOC cells was also significantly downregulated in this process. The metastasis of EOC cells was correlated with the levels of TGF‐β1 or IL‐10. These findings suggested that immunosuppressive cytokines secreted by CD4+ Tregs could be a novel target for inhibiting EOC progression.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting cytokines secreted by CD4⁺CD25^highCD127^low regulatory T cells inhibits ovarian cancer progression

Xing

Shen

2018

Scand J Immunol

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“…ТІМП відіграють важливу роль у регуляції широкого спектру клітинних процесів, беруть участь у контролі та ремоделюванні позаклітинного матриксу, міжклітинній адгезії та сигналингу (із залученням факторів росту) тощо [24]. Активація ММП у позаклітинному матриксі специфічно подавляється ендогенними тканинними інгібіторами металопротеїназ (TІМП) завдяки формуванню стійких і необоротних нековалентних зв'язків із метал-зв'язувальними ділянками активних ММП в еквімолярному співвідношенні.…”

Section: т а б л и ц я 3 вміст ммп-3 у тканинах пухлинunclassified

The content of matrix metalloproteinases in bladder cancer tumors

2019

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Bladder cancer (BC) is the 9th in frequency oncologic disease, with the highest number of patients in developed countries. The disease is more commonly diagnosed in men – about 75%. The ability to invade surrounding tissues and metastasis to individual organs is one of the fundamental properties of malignant tumors. According to modern ideas about mechanisms of metastasis, basement membranes and extracellular matrix are the main barriers, and tissue structures are needed to overcome the invasive growth of tumor cells. Almost all of the extracellular matrix components can be destroyed by the use of metal-matrix proteinases (MMP), moreover, the precursors of growth factors and adhesion molecules on the cell surface may be the MMP substrates. MMPs also participate in epithelial-mesenchymal transformation, which provides metastasis. Previous studies by other authors point to an increase in the biosynthesis of various MMPs in the outbreak of tumors and in metastases, such changes associated with the degree of differentiation of the tumor, the depth of the invasion, as well as their association with poor further prognosis and low survival rates in patients with various cancers. The purpose of our work was to investigate the content of MMP-1, 2, 3, 8 and TIMP-1 in the tumors and walls of the healthy bladder in patients with BC, depending on the stage of TNM classification. We investigated the increase in the content of MMP-1, 2, 3, 8 and TIMP-1 in samples of healthy bladder walls for stage 3 and 4 of the BC, indicating the participation of the investigated parameters in the growth and invasion of bladder tumors. The results of our study are consistent with the results of previous studies conducted in the study of other neoplasms, which indicate the relationship between the studied parameters with the development of cancer.

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“…In addition, matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) and cellular components in the tissue microenvironment, are closely associated with cancer cell growth and progression as well as normal tissue remodelling . High expression and activity of MMPs have been reported to contribute to aggressive phenotypes and poor survival of ovarian cancer . However, inhibition of MMP activity without sufficient knowledge about substrate specificity or physiological roles in cancer biology has been disappointing in various cancer clinical trials .…”

Section: Introductionmentioning

confidence: 99%

“…6,7 High expression and activity of MMPs have been reported to contribute to aggressive phenotypes and poor survival of ovarian cancer. 8,9 However, inhibition of MMP activity without sufficient knowledge about substrate specificity or physiological roles in cancer biology has been disappointing in various cancer clinical trials. 10 Therefore, intensive investigations of cellular and molecular networks underlying the progression of ovarian cancer may provide insights into effective therapeutic targets and strategies for the prevention and treatment of cancer.…”

mentioning

confidence: 99%

Novel functions for 2‐phenylbenzimidazole‐5‐sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis

Kim

Ahn

et al. 2020

J Cellular Molecular Medi

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In this study, we investigated the effects and molecular mechanisms of 2‐phenylbenzimidazole‐5‐sulphonic acid (PBSA), an ultraviolet B protecting agent used in sunscreen lotions and moisturizers, on ovarian cancer cell responses and tumour angiogenesis. PBSA treatment markedly blocked mitogen‐induced invasion through down‐regulation of matrix metalloproteinase (MMP) expression and activity in ovarian cancer SKOV‐3 cells. In addition, PBSA inhibited mitogen‐induced cell proliferation by suppression of cyclin‐dependent kinases (Cdks), but not cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. These anti‐cancer activities of PBSA in ovarian cancer cell invasion and proliferation were mediated by the inhibition of mitogen‐activated protein kinase kinase 3/6‐p38 mitogen‐activated protein kinase (MKK3/6‐p38MAPK) activity and subsequent down‐regulation of MMP‐2, MMP‐9, Cdk4, Cdk2 and integrin β1, as evidenced by treatment with p38MAPK inhibitor SB203580. Furthermore, PBSA suppressed the expression and secretion of vascular endothelial growth factor in SKOV‐3 cells, leading to inhibition of capillary‐like tubular structures in vitro and angiogenic sprouting ex vivo. Taken together, our results demonstrate the pharmacological effects and molecular targets of PBSA on modulating ovarian cancer cell responses and tumour angiogenesis, and suggest further evaluation and development of PBSA as a promising chemotherapeutic agent for the treatment of ovarian cancer.

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

Cited by 42 publications

References 39 publications

Targeting cytokines secreted by CD4⁺CD25^highCD127^low regulatory T cells inhibits ovarian cancer progression

Targeting cytokines secreted by CD4⁺CD25^highCD127^low regulatory T cells inhibits ovarian cancer progression

The content of matrix metalloproteinases in bladder cancer tumors

Novel functions for 2‐phenylbenzimidazole‐5‐sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis

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

Cited by 42 publications

References 39 publications

Targeting cytokines secreted by CD4+CD25highCD127low regulatory T cells inhibits ovarian cancer progression

Targeting cytokines secreted by CD4+CD25highCD127low regulatory T cells inhibits ovarian cancer progression

The content of matrix metalloproteinases in bladder cancer tumors

Novel functions for 2‐phenylbenzimidazole‐5‐sulphonic acid: Inhibition of ovarian cancer cell responses and tumour angiogenesis

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Product

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Targeting cytokines secreted by CD4⁺CD25^highCD127^low regulatory T cells inhibits ovarian cancer progression

Targeting cytokines secreted by CD4⁺CD25^highCD127^low regulatory T cells inhibits ovarian cancer progression