TIMP-2 inhibits metastasis and predicts prognosis of colorectal cancer via regulating MMP-9

Wang, Weimin; Li, Dan; Xiang, Lei; Lv, Mengying; Li, Tao; Ni, Tengyang; Deng, Jianliang; Gu, Xiang; Masatara, Sunagawa; Liu, Yanqing; Zhou, Yan

doi:10.1080/19336918.2019.1639303

Cited by 46 publications

(41 citation statements)

References 39 publications

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“…Correspondingly, in case of HSF and OR inhibition to (active) MMP‐2 secretion, with no LPS responsiveness, might possibly be associated with an increase of TIMP‐2 levels as well. The last publication reported that decreased levels of TIMP‐2 were closely related to poor prognosis of CRC metastasis (Wang et al., 2019),…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of a gamma‐oryzanol‐rich fraction from purple rice extract on lipopolysaccharide‐induced metastasis in human colon cancer cells

Panyathep

Chewonarin

2020

J. Food Biochem.

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The incidence of colon cancer recurrence and metastasis is known to increase as an adverse effect related to postoperative infection. Lipopolysaccharide or LPS, which is derived from gram-negative bacteria, is a key inducer of inflammatory-related tumor metastasis. Although there are numerous known biological effects of purple rice extract (PRE), its protective effect on colon metastasis was unknown. This study first evaluated the effects of hexane soluble fraction (HSF) or γ-oryzanol-rich fraction of PRE on LPS-induced colon cancer adhesion and invasion, which was accomplished using adhesive and invasive assay. Gelatin zymography was also utilized for gelatinase activity and secretion. Its chelating activity was also further analyzed by reverse gelatin zymography with zinc chloride. The study findings support the synergistic effect of HSF in protection against adverse events from LPS-induced colon cancer metastasis, as shown by effects on adhesive and invasive ability as well as matrix metalloproteinase-2 secretion and activity. Practical applications Bacterial infection is still one of the main adverse events following abdominal cancer surgery and is associated with an increased incidence of colon cancer metastasis. Lipopolysaccharide (LPS) is a major component of this pathogen-mediated response. This first study investigated the efficiency of a gamma-oryzanol (OR) rich fraction, collected from purple rice extract (PRE), against LPS-induced colon cancer metastasis that occurs via three main steps; adhesion to the extracellular matrix, the secretion, and activity of gelatinase and further tissue invasion. The acquired data supported the role of an OR-rich fraction from PRE as a potential inhibitor to LPS-induced colon cancer progression. This finding, related to PRE, could be further developed to create a new adjunctive treatment to reduce operative complications related to bowel cancer surgery as well as increasing the value of this crop in Thailand.

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Section: Discussionmentioning

confidence: 99%

Inhibitory effect of a gamma‐oryzanol‐rich fraction from purple rice extract on lipopolysaccharide‐induced metastasis in human colon cancer cells

Panyathep

Chewonarin

2020

J. Food Biochem.

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“…Interestingly, TIMP-2, tissue inhibitor of metalloproteinases (TIMPs) family, has also been identified in our study. TIMP-2 was described to decrease cell proliferation and migration in vitro via the inhibition of MMPs ( 46 ). However, it is associated with poor patient outcomes in cancers including gastric ( 47 ), renal ( 48 ), and oral squamous cell cancers ( 49 ).…”

Section: Discussionmentioning

confidence: 99%

Schwann Cell Stimulation of Pancreatic Cancer Cells: A Proteomic Analysis

Ferdoushi

Griffin

et al. 2020

Front. Oncol.

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Schwann cells (SCs), the glial component of peripheral nerves, have been identified as promoters of pancreatic cancer (PC) progression, but the molecular mechanisms are unclear. In the present study, we aimed to identify proteins released by SCs that could stimulate PC growth and invasion. Proteomic analysis of human primary SC secretome was performed using liquid chromatography-tandem mass spectrometry, and a total of 13,796 unique peptides corresponding to 1,470 individual proteins were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were conducted using the Database for Annotation, Visualization, and Integrated Discovery. Metabolic and cell-cell adhesion pathways showed the highest levels of enrichment, a finding in line with the supportive role of SCs in peripheral nerves. We identified seven SC-secreted proteins that were validated by western blot. The involvement of these SC-secreted proteins was further demonstrated by using blocking antibodies. PC cell proliferation and invasion induced by SC-conditioned media were decreased using blocking antibodies against the matrix metalloproteinase-2, cathepsin D, plasminogen activator inhibitor-1, and galectin-1. Blocking antibodies against the proteoglycan biglycan, galectin-3 binding protein, and tissue inhibitor of metalloproteinases-2 decreased only the proliferation but not the invasion of PC cells. Together, this study delineates the secretome of human SCs and identifies proteins that can stimulate PC cell growth and invasion and therefore constitute potential therapeutic targets.

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“…G-CSF has a role in granulopoiesis and anti-inflammation. 29 TIMP-2 30,31 and TGF-b are mildly elevated. 32 TIMP2 actively attenuates the negative remodelling and TGFb2 is involved in tissue repair.…”

Section: Elevated Cytokinesmentioning

confidence: 97%

Rose Extract Treatment on the CD4+ T lymphocytes

Arokiaraj¹,

Menesson²

2021

Preprint

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Background and Aims:To study the effect of rose extract on CD4 T lymphocytes, and assess the cytokines response after cell treatment. In our previous study on endothelial cells, the rose extract reduced the secretion of inflammatory markers significantly. Methods:The red rose extract used in this study was prepared and stored until use at -20 degree C. T cells were seeded in 96-well plates at 313500 cells/well in 100microl of cell culture medium in duplicate, one half of the wells were used for biomarkers screening in the culture medium, and the other half for cytotoxicity assay. 24h after plating, the cells were treated in duplicate with 100microl of red rose extract diluted at 0.5%, 0.1%, 0.05%, 0.01% and 0.005% (v/v) in cell culture medium or with culture medium only as control for 72h. Some other wells were for untreated cells, and cells treated with rose extract at 0.005% for 48h incubation time. After 48h and 72h, the corresponding wells were used for the cytotoxicity assay and from the duplicate wells, the cell culture media were collected and stored at -80degree C until the biomarkers screening assay. Results:Cytotoxicity assay revealed insignificant changes. IFN-gamma, MCP-1, GRO, RANTES and TIMP, Angiopoietin 1 and MMP-9 were elevated. Except MMP-9 which had fold changes >2 other cytokines were minimally elevated at various concentrations and timing of rose extract treatment. None of the cytokines were less than 0.8 fold. Conclusions:Unlike in the endothelial cells, there is mild elevation in few inflammatory markers on T lymphocytes treatment by rose extract. Further studies need to be performed to estimate the clinical relevance.

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TIMP-2 inhibits metastasis and predicts prognosis of colorectal cancer via regulating MMP-9

Cited by 46 publications

References 39 publications

Inhibitory effect of a gamma‐oryzanol‐rich fraction from purple rice extract on lipopolysaccharide‐induced metastasis in human colon cancer cells

Inhibitory effect of a gamma‐oryzanol‐rich fraction from purple rice extract on lipopolysaccharide‐induced metastasis in human colon cancer cells

Schwann Cell Stimulation of Pancreatic Cancer Cells: A Proteomic Analysis

Rose Extract Treatment on the CD4+ T lymphocytes

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