Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer

Kushlinskii, N. E.; Es, Gershteĭn; Иванников, А. А.; Давыдов, М. М.; Chang, V L; Огнерубов, Н.А.; Стилиди, И. С.

doi:10.1007/s10517-019-04353-y

Cited by 10 publications

(7 citation statements)

References 10 publications

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“…Matrix metalloproteinase-7 (MMP-7) is an enzyme responsible for the degradation of adherence between cells in the extracellular matrix, and overexpression of MMP-7 induces a more aggressive course of gastric cancer [270][271][272][273]. MMP-7 and HB-EGF expression is upregulated by H. pylori infection and is associated with EMT [274,275]. Likewise, MMP-7 overexpression is because of increased levels of gastrin, activator protein 1 (AP-1), and NF-kB induced by H. pylori infection [276][277][278][279].…”

Section: Heparin-binding Epidermal Growth Factor and Matrix Metalloprmentioning

confidence: 99%

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Baj

Korona-Głowniak

Forma

et al. 2020

Cells

118

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Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.

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Section: Heparin-binding Epidermal Growth Factor and Matrix Metalloprmentioning

confidence: 99%

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Baj

Korona-Głowniak

Forma

et al. 2020

Cells

118

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“…MMP expression is involved in the invasion and metastasis of malignant tumors, and is induced in H. pylori-infected gastric epithelial cells [5][6][7][8][9][10]. High levels of plasma MMPs were found in gastric cancer patients and, therefore, MMPs could serve as important diagnostic markers of gastric cancer [39]. MMP-10 is upregulated via ERK signaling in H. pylori-infected AGS cells [10].…”

Section: Discussionmentioning

confidence: 99%

β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in Helicobacter pylori-Infected Gastric Epithelial Cells

2021

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Matrix metalloproteinases (MMPs), key molecules of cancer invasion and metastasis, degrade the extracellular matrix and cell–cell adhesion molecules. MMP-10 plays a crucial role in Helicobacter pylori-induced cell-invasion. The mitogen-activated protein kinase (MAPK) signaling pathway, which activates activator protein-1 (AP-1), is known to mediate MMP expression. Infection with H. pylori, a Gram-negative bacterium, is associated with gastric cancer development. A toxic factor induced by H. pylori infection is reactive oxygen species (ROS), which activate MAPK signaling in gastric epithelial cells. Peroxisome proliferator-activated receptor γ (PPAR-γ) mediates the expression of antioxidant enzymes including catalase. β-Carotene, a red-orange pigment, exerts antioxidant and anti-inflammatory properties. We aimed to investigate whether β-carotene inhibits H. pylori-induced MMP expression and cell invasion in gastric epithelial AGS (gastric adenocarcinoma) cells. We found that H. pylori induced MMP-10 expression and increased cell invasion via the activation of MAPKs and AP-1 in gastric epithelial cells. Specific inhibitors of MAPKs suppressed H. pylori-induced MMP-10 expression, suggesting that H. pylori induces MMP-10 expression through MAPKs. β-Carotene inhibited the H. pylori-induced activation of MAPKs and AP-1, expression of MMP-10, and cell invasion. Additionally, it promoted the expression of PPAR-γ and catalase, which reduced ROS levels in H. pylori-infected cells. In conclusion, β-carotene exerts an inhibitory effect on MAPK-mediated MMP-10 expression and cell invasion by increasing PPAR-γ-mediated catalase expression and reducing ROS levels in H. pylori-infected gastric epithelial cells.

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“…Следует отметить, что уровень ММП-7 в периферической крови повышается и имеет прогностическое значение не только при раке почки, но и при некоторых других злокачественных новообразованиях [6,10,13,14], что указывает на универсальный характер этих изменений и может быть обусловлено тем, что ММП-7 -единственный представитель данного семейства, который секретируется преимущественно опухолевыми, а не стромальными клетками. Универсальность повышения ММП-7 в сыворотке и плазме крови при опухолях различного гистогенеза не позволяет рекомендовать ММП-7 в качестве специфического диагностического маркера.…”

Section: заключениеunclassified

“…Тканевая экспрессия отдельных ММП, ТИМП и показателей системы VEGF/ VEGFR имеет диагностическое и прогностическое значение при некоторых типах опухолей. Проводятся также исследования клинического значения компонентов сигнальной системы VEGF и ММП/ТИМП, циркулирующих в периферической крови, однако их результаты пока неоднозначны [3][4][5][6][7][8][9][10].…”

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Key VEGF signaling system components and matrix metalloproteinases in the diagnosis and prognosis of overall survival of patients with renal cell cancer

Kushlinskii¹,

Герштейн²,

Колпаков

et al. 2020

Alʹm. klin. med.

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Background: Evaluation and search for new molecular markers of renal cell cancer, first of all, associated with angiogenic and invasive activity, continue to be highly relevant. In our previous publications, we have assessed the potential diagnostic value of matrix metalloproteinases (MMP) 2, 7, 8, and 9, their tissue inhibitor type 1 (TIMP1) and components of the VEGF signaling system in renal cell cancer.Aim: To assess the role of serum VEGF, VEGFR1, VEGFR2, MMP2, 7, 8, 9, and TIMP1 levels in renal cell patients as diagnostic and prognostic markers of overall survival.Materials and methods: 99 renal cell cancer patients (94 primary and 5 at progression) were recruited into the study. The control group included 97 healthy control blood donors. Ninety three (93) primary patients with renal cell cancer were followed for 1 to 45 (median, 26) months for assessment of their overall survival. Serum concentrations of the study proteins were measured by direct immunoenzyme analysis (Quantikine® ELISA kits, R&D Systems, USA).Results: Serum VEGF, VEGFR1, VEGFR2, MMP7, MMP8, and TIMP1 levels in renal cell cancer patients are significantly higher than those in the control group. The diagnostic characteristics of the markers are considerably different, the most reliable marker with 84% sensitivity at 87.5% specificity being MMP7. VEGFR1, MMP7, MMP8, and TIMP1 were positively associated with disease stage and TNM indices. MMP7 and TIMP1 levels also increased with a higher tumor grade. MMP7 was found to be a significant unfavorable prognostic factor for overall survival: the 3-years survival in those with low (<6.3 ng/ml) marker level amounted to 93%, whereas with high, 51% (p<0.001). MMP7 prognostic value remained significant also in stage I renal cancer: after 3-years' follow-up, all patients with low MMP7 were alive, while survival of those with high marker levels was 72% (p=0.02). Increased serum MMP8 level (>51 ng/ml) also had an unfavorable prognostic value in the whole renal cell cancer patient group, with 3-years' survival being 78 and 58% for low and high levels, respectively (p<0.01). The components of VEGF signaling system, MMP2, MMP9, and TIMP1 had no significant prognostic values.Conclusion: MMP7 should be viewed as the most promising diagnostic and prognostic renal cell cancer marker. VEGF and its soluble receptors could be useful for monitoring of patients receiving anti-angiogenic treatments and prediction of their sensitivity to these agents.

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Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer

Cited by 10 publications

References 10 publications

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

β-Carotene Inhibits Expression of Matrix Metalloproteinase-10 and Invasion in Helicobacter pylori-Infected Gastric Epithelial Cells

Key VEGF signaling system components and matrix metalloproteinases in the diagnosis and prognosis of overall survival of patients with renal cell cancer

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