Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients

Groblewska, Magdalena; Mroczko, Barbara; Gryko, Mariusz; Pryczynicz, Anna; Guzińska‐Ustymowicz, Katarzyna; Kędra, Bogusław; Kemonä, A; Szmitkowski, Maciej

doi:10.1007/s13277-013-1502-8

Cited by 58 publications

(47 citation statements)

References 29 publications

(36 reference statements)

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“…For instance, increased TIMP-1 and TIMP-2 are associated with a poor prognosis in patients, which are produced by colon cancer cells and adjacent stroma cells. 48–50 Notably, our data reveal for the first time that primary human MC are able to express and secrete both TIMP-1 and TIMP-2. In addition, uPAR expression, especially in tumor-associated stromal cells, is negatively associated with CRC patient survival 51 and MIF can promote intestinal inflammation and colonic carcinogenesis.…”

Section: Discussionmentioning

confidence: 67%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

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Chronic inflammation drives the development of colorectal cancer (CRC), where tumor-infiltrating immune cells interact with cancer cells in a dynamic crosstalk. Mast cells (MC), one of earliest recruited immune cells, accumulate in CRC tissues and their density is correlated with cancer progression. However, the exact contribution of MC in CRC and their interaction with colon cancer cells is poorly understood. Here, we investigated the impact of primary human MC and their mediators on colon cancer growth using 2D and 3D coculture models. Primary human MC were generated from peripheral CD34+ stem cells. Transwell chambers were used to analyze MC chemotaxis to colon cancer. Colon cancer cells HT29 and Caco2 differentially recruited MC by releasing CCL15 or SCF, respectively. Using BrdU proliferation assays, we demonstrated that MC can directly support colon cancer proliferation and this effect was mediated by their cellular crosstalk. 3D coculture models with cancer spheroids further confirmed the pro-tumor effect of MC on colon cancer growth, where direct cell-cell contact is dispensable and increased production of multiple soluble mediators was detected. Moreover, TLR2 stimulation of MC promoted stronger growth of colon cancer spheroids. By examining the transcriptome profile of colon cancer-cocultured MC versus control MC, we identified several MC marker genes, which were deregulated in expression. Our study provides an advanced in vitro model to investigate the role of human MC in cancer. Our data support the detrimental role of MC in CRC development and provide a molecular insight into the cellular crosstalk between MC and colon cancer cells.

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Section: Discussionmentioning

confidence: 67%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

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“…These proteases facilitate cancer cell metastasis by degrading the basement membranes. Matrix metalloproteinase-2 (MMP-2) and MMP-9 play important roles in CRC and are considered to correlate with the prognosis of patients [4,5]. Decreased MMP-9 expression level was reported to associate with longer survival time and lower risk of cancer recurrence [6].…”

Section: Introductionmentioning

confidence: 99%

Matrine reduces the proliferation and invasion of colorectal cancer cells via reducing the activity of p38 signaling pathway

Ren¹,

Zhang²,

Ma³

et al. 2014

ABBS

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Matrine has been used in anti-inflammatory and anti-cancer therapies for a long time. However, the anti-metastatic effect and related mechanism(s) in colorectal cancer (CRC) are still unclear. In this study, we investigated whether the administration of matrine could inhibit the proliferation, motility, and invasion of human CRC cells via regulating p38 signaling pathway. Results showed that matrine inhibited migration and invasion of CRC cells in vitro and in vivo. Additionally, after being treated with matrine for 24 h, the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 as well as proteinase activity in CRC cells were reduced in a dose-dependent manner. Moreover, matrine reduced the phosphorylation level of p38 obviously. Combined treatment with p38 inhibitor (SB203580) and matrine resulted in a synergistic reduction of invasion as well as MMP-2/-9 expression in CRC cells. It was also found that matrine inhibited the proliferation and metastasis of CRC tumor in vivo. In conclusion, p38 signaling pathway may involve in matrine's inhibitory effects on migration and invasion of CRC cells by reducing the expression of MMP-2/-9, suggesting that matrine may be a potential therapeutic agent for CRC.

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“…These enzymes could, therefore, represent an appealing target for the proteolytic degradation of our microswimmers once they have completed their prescribed tasks. In a healthy individual, this enzyme is reportedly present at various concentrations, yet typically in the range of 140-200 ng mL -1 , depending on type of the tissue it is expressed (40,41). At an unrealistically high concentration of MMP-2, i.e., 100 µg mL -1 , we observed that the microswimmers were entirely degraded within an hour in vitro at 37 °C (Supplementary Movie 3).…”

Section: Biodegradability With Mmp-2mentioning

confidence: 81%

3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling

Ceylan

Yasa

Yaşa

et al. 2018

Preprint

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Miniaturization of interventional medical devices can leverage minimally invasive technologiesby enabling operational resolution at cellular length scales with high precision and repeatability.Untethered micron-scale mobile robots can realize this by navigating and performing in hard-toreach, confined and delicate inner body sites. However, such a complex task requires an integrated design and engineering strategy, where powering, control, environmental sensing, medical functionality and biodegradability need to be considered altogether. The present study reports a hydrogel-based, biodegradable microrobotic swimmer, which is responsive to the changes in its microenvironment for theranostic cargo delivery and release tasks. We design a double-helical magnetic microswimmer of 20 µm length, which is 3D-printed with complex geometrical and compositional features. At normal physiological concentrations, matrix metalloproteinase-2 (MMP-2) enzyme can entirely degrade the microswimmer body in 118 h to solubilized non-toxic products. The microswimmer can respond to the pathological concentrations of MMP-2 by swelling and thereby accelerating the release kinetics of the drug payload. Anti-ErbB 2 antibodytagged magnetic nanoparticles released from the degraded microswimmers serve for targeted labeling of SKBR3 breast cancer cells to realize the potential of medical imaging of local tissue sites following the therapeutic intervention. These results represent a leap forward toward clinical medical microrobots that are capable of sensing, responding to the local pathological information, and performing specific therapeutic and diagnostic tasks as orderly executed operations using their smart composite material architectures.

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Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients

Cited by 58 publications

References 29 publications

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Matrine reduces the proliferation and invasion of colorectal cancer cells via reducing the activity of p38 signaling pathway

3D-Printed Biodegradable Microswimmer for Drug Delivery and Targeted Cell Labeling

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