MMI-166, a selective matrix metalloproteinase inhibitor, promotes apoptosis in human pancreatic cancer

Gao, Chong; Gong, Bo; Wu, Jun-ben; Cheng, Pi-guang; Xu, Huai-yong; Song, Dekun; Li, Fēi

doi:10.1007/s12032-014-0418-5

Cited by 4 publications

(4 citation statements)

References 17 publications

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“…Although broad spectrum MMP inhibitors limit PDAC progression in preclinical animal models [73][74][75][76][77][78][79][80][81][82], they seem to lack efficacy in a clinical setting [115,116]. This disparity between preclinical data and clinical trials can be attributed to several factors-for instance, differences in pharmacokinetics, pharmacodynamics and metabolism and the failure to accurately model the tumor microenvironment [128].…”

Section: Discussionmentioning

confidence: 99%

“…The potential importance of MMP2 and MMP9 in PDAC progression is further supported by studies using more specific inhibitors like MMI-166, RO28-2653 and OPB-3206. Indeed, the selective MMP2, MMP9 and MMP14 inhibitor MMI-166 inhibited PDAC growth in both mice and Syrian hamsters [79,80], whereas RO28-2653 and OPB-3206 (both also selective MMP2, MMP9 and MMP14 inhibitors) reduced chemically induced pancreatic carcinogenesis in Syrian hamsters [81,82]. Finally, treatment with the selective MMP2 and MMP9 inhibitor SB-3CT reduced the lung metastasis of subcutaneously implanted PDAC cells [83].…”

Section: Gelatinases In Pdacmentioning

confidence: 98%

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Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Slapak

Duitman

Tekin

et al. 2020

Biology

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Pancreatic cancer is a dismal disorder that is histologically characterized by a dense fibrotic stroma around the tumor cells. As the extracellular matrix comprises the bulk of the stroma, matrix degrading proteases may play an important role in pancreatic cancer. It has been suggested that matrix metalloproteases are key drivers of both tumor growth and metastasis during pancreatic cancer progression. Based upon this notion, changes in matrix metalloprotease expression levels are often considered surrogate markers for pancreatic cancer progression and/or treatment response. Indeed, reduced matrix metalloprotease levels upon treatment (either pharmacological or due to genetic ablation) are considered as proof of the anti-tumorigenic potential of the mediator under study. In the current review, we aim to establish whether matrix metalloproteases indeed drive pancreatic cancer progression and whether decreased matrix metalloprotease levels in experimental settings are therefore indicative of treatment response. After a systematic review of the studies focusing on matrix metalloproteases in pancreatic cancer, we conclude that the available literature is not as convincing as expected and that, although individual matrix metalloproteases may contribute to pancreatic cancer growth and metastasis, this does not support the generalized notion that matrix metalloproteases drive pancreatic ductal adenocarcinoma progression.

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Section: Discussionmentioning

confidence: 99%

Section: Gelatinases In Pdacmentioning

confidence: 98%

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Slapak

Duitman

Tekin

et al. 2020

Biology

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“…Both the tumor cells and surrounding stromal cells can synthesize MMPs [29]. MMP9 is one of the key proteolytic enzymes in the breakdown and reconstruction of the extracellular matrix in colorectal cancer (CRC) invasion and metastasis [30]. TNF-α upregulates MMP9 expression via c-Src, MAPKs, and NF-κB pathways [31].…”

Section: Discussionmentioning

confidence: 99%

Diabetes mellitus induces a novel inflammatory network involving cancer progression: Insights from bioinformatic analysis and in vitro validation

Tan

Kang

Liu

et al. 2022

Preprint

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Background The diabetes patients have a higher incidence of malignant tumors than people without diabetes. However, the molecular mechanisms of the relationship between diabetes and malignant tumors remain largely unknown. Methods By exploiting available public databases, diabetes and cancer-related genes (DCRGs) were screened, and a diabetes-based cancer-associated inflammation network (DCIN) was constructed. Then, the role of DCRGs in different tumors were analyzed from various perspectives. Additionally, drug sensitivity and single-cell sequencing data were analyzed using colon cancer (COAD) as an example. Finally, the expression of DCRGs and arachidonic acid metabolism pathway was verified in vitro. Results Seven identified DCRGs, including PPARG, MMP9, CTNNB1, TNF, TGFB1, PTGS2, and HIF1A, were integrated to construct a DCIN. The bioinformatics analysis showed that the expression of the seven DCRGs in different tumors was significantly different, which had varied effects on diverse perspectives. Single-cell sequencing analyzed in COAD showed that the activity of the DCRGs was highest in M1 macrophage and the lowest in Plasma B. In vitro experiments showed that the DCRGs verified by western bolt and PEG2 verified by ELISA were all highly expressed in COAD epithelial cells stimulated by high glucose. Conclusion This study, for the first time, constructed a DCIN, which provides novel insights into the underlying mechanism of how diabetes increases the occurrence and development of tumors. Although further research is required, our results offer clues for new potential therapeutic strategies to prevent and treat malignant tumors.

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“…MMP-9 is also active in the formation of early metastatic niches [ 8 ]. In preclinical models, selective MMP-9 inhibitors have been shown to decrease tumor growth and the incidence of metastases in colorectal cancer and also induce cancer cell apoptosis in pancreatic cancer [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer

et al. 2018

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Matrix metalloproteinases (MMPs) are believed to be of importance in the growth and spread of colorectal cancer (CRC). MMP-9 level has been suggested as a biological predictor of prognosis in CRC as well as in other types of cancer such as breast and cervical cancer. The purpose of this study was to investigate the stability over time of MMP-9 in cryopreserved plasma, colorectal tumor tissue extract and macroscopically tumor-free colon mucosa tissue extract samples. Plasma and tissue samples were taken from patients at primary CRC surgery and analyzed for MMP-9. Aliquots of samples from the same patients were stored at – 80 °C pending analysis. These aliquots were analyzed using identical methods after storage periods of nine (plasma) and twelve (tissue) years. No significant difference in plasma MMP-9 concentration was seen between baseline samples and those after 9 years of cryopreservation (median values 9.9 and 9.7 ng/mL, respectively; p > 0.05). MMP-9 levels in the tumor-free tissue extracts had increased to baseline (median values 7.1 and 8.1 ng/mL, respectively; p < 0.01). MMP-9 levels in the tumor tissue extracts had also increased significantly (median values 89.9 and 133.5 ng/mL, respectively; p < 0.01). We have demonstrated that MMP-9 levels in frozen citrated plasma are stable if stored at − 80 °C, whereas MMP-9 levels in extracts from tumor tissue and tumor-free intestinal mucosa appear to increase with time. We conclude that MMP-9 levels in cryopreserved plasma may be considered stable over time and are thus suitable for comparison purposes in consecutive series.

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MMI-166, a selective matrix metalloproteinase inhibitor, promotes apoptosis in human pancreatic cancer

Cited by 4 publications

References 17 publications

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Matrix Metalloproteases in Pancreatic Ductal Adenocarcinoma: Key Drivers of Disease Progression?

Diabetes mellitus induces a novel inflammatory network involving cancer progression: Insights from bioinformatic analysis and in vitro validation

Stability of matrix metalloproteinase-9 as biological marker in colorectal cancer

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