Herein we describe construction of a nanosensor for matrix metalloproteinase 9 (MMP9), which is associated with tumor progression and metastasis, for detection of colorectal cancer in a mouse model.
In these cancers, up-regulation of trafficking and secretion of matrix metalloproteinase-9 (MMP-9), a proteolytic enzyme, is responsible for degrading the extracellular matrix, a necessary step in tumor progression.
The changes of tumor volume, body weight, NF-κB activation, MAPK activation, and tumor progression-associated proteins (MMP-9, XIAP, VEGF, and Cyclin-D1) after regorafenib treatment were evaluated with digital caliper, digital weight, and ex vivo Western blotting assay.
These data suggest that in vivo MMP9-mediated processing of HSPB1 acts to regulate VEGF-induced ECs activation for tumor progression, releasing anti-angiogenic HSPB1 fragments.
We previously showed that enhanced expression of MMP-9, an endopeptidase that digests basement-membrane type IV collagen, is related to tumor progression in vitro and in vivo; antisense-MMP-9 stably transfected clones were less invasive than untransfected parental cells and did not form tumors in nude mice.
Our previous studies have reported that urokinase plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) play important roles in tumor progression.
This process includes the induction of Smad2/3 phosphorylation, the increase of Smad2/3 transcriptional activity and the upregulation of the expression of target genes involved in EMT and cancer progression (such as TGF-β1, MMP-2, MMP-9, plasminogen activator inhibitor type-1, vascular endothelial growth factor, Snail and Slug), thus promoting cancer cell mobility and invasion.
MMP-9 plays important roles in the breakdown of the extracellular matrix and in the facilitation of tumor progression, invasion, metastasis, and angiogenesis.
Taken together, the data show that in neuroblastoma, MMP-9 plays a critical role in the recruitment of bone marrow-derived cells to the tumor microenvironment where they positively contribute to angiogenesis and tumor progression.
MMP9 promotes local tumor progression and distant metastasis in mouse models by enhancing extracellular matrix degradation, releasing VEGF from extracellular matrix and promoting vascular pericyte recruitment.
The expression of mRNA and proteins involved in migration and cancer progression [epithelial cell adhesion molecule, intercellular adhesion molecule-1, β-catenin, N-cadherin, E-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9] was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis.
Taken together, our findings suggest that the TGFβ1 and the MMP-9 feedback loop is critical in tumor progression, as it may aid in the development of treatment strategies that are designed to target both TGFβ and MMP-9.
At the same time, cIAP1 downregulation decreased the secretion of MMP-9. shRNA depletion of cIAP1 enhanced chemosensitivity of ovarian cancer cells to Taxol and carboplatin-induced apoptosis. cIAP1 is associated with tumor progression in human ovarian cancer.
In addition, silencing of CtBP2 markedly increased the apoptosis of PCa cells in vitro, and decreased the expression of IL-8, AT2R, CCND1 and MMP9 which are associated with cancer progression.