CA can act by preventing the production of ROS (reactive oxygen species), inducing DNA oxidation of cancer cells, as well as reducing tumor cell angiogenesis, blocking STATS (transcription factor and signal translation 3) and suppression of MMP2 and MMP-9 (collagen IV metalloproteases).
The ipsilateral hemisphere with MBD-EPO (vs. MBD-only) showed significantly increased vessels (RECA-1, p = 0.0182) and their maturation (RECA-1/α-SMA, p = 0.0046), with upregulation of tumor growth factor-β1 (Tgf-β1, p = 0.037) and matrix metalloproteinase-2 (Mmp-2, p = 0.0488).
<b>Conclusion:</b> The developed multifunctional Au PENPs are a promising theranostic platform for targeted imaging and treatment of different MMP2-overexpressing tumors.
Silencing the α7-nAChR reduced the viability of HCC cells, suppressed cellular proliferation, attenuated migration and invasion, and diminished the tumor's sphere-formation ability, with concurrent downregulation of expression levels of the TGR5, p-JAK2, p-STAT3 (Tyr705/Ser727), RhoA, ROCK1, MMP2, and MMP9 proteins.
In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2.
As gelatin is a substrate of tumor extracellular metal matrix protease-2 (MMP2), GNPs-P-Dox-GA nanoparticles could be degraded and release small size P-Dox-GA to facilitate tumor tissue penetration.
In the validation cohort, however, only the changes in the plasma levels of CXCL2 and MMP2 after treatment were associated with PFS (p = 0.003 and p = 0.006, respectively), and these changes were maintained during the course of anti-PD-1 therapy in patients who showed better clinical outcomes, even in those with tumor pseudoprogression.
Clear evidence was shown in vitro and in vivo to demonstrate that this multifunctional protein fusing a pro-apoptotic KLAKLAKKLAKLAK (KLA), named PAK, can increase circulation time in blood, enhance accumulation at tumor sites, eliminate the PsTag domain and the polyanionic sequence when triggered by tumor overexpressing MMP2, and then expose the cell penetrating peptide to realize the potent cellular uptake of KLA.
After accumulation at the tumor site, in response to overexpressed matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment, gemcitabine (GEM)-conjugated small nanoparticles (DGL/GEM) are released from DGL/GEM@PP/GA, leaving 18β-glycyrrhetinic acid (GA)-loaded large nanoparticles (PP/GA).
Compared with the control group, the tumor tissues from mice in the LOX inhibition group had reduced relative expression levels and enzyme activities of MMP-2 and MMP-9 (P < 0.05).
Significant overexpression of MMP-2 in tumor and normal tissue was correlated with advanced stages, tumor size, sarcomatous differentiation and clinical symptoms.
We investigate redox state-superoxide (SO) generation rate, activity of complex I in electron transport chain (ETC) of mitochondria and of dinitrosyl iron complexes by electron paramagnetic resonance; activity of matrix metalloproteinase (gelatinase) MMP-2 and MMP-9 by gel zymography of adipose tissues (AT) from 46 patients (64.0 ± 1.6 y.o.) with CRC (II-III stages, pT2-3N0-2M0) in the AT adjacent to tumor (ATAT) and at a distance of 3 cm from the tumor (ATD) to follow the connection of the AT redox state with some of the tumor microenvironment indicators.
Bio-informatics prediction and our experiments validated that MMP-2 and MMP-9 were simultaneously targeted by miR-296-3p and FOXC1 promoter upstream transcript (FOXCUT); the latter two exerted tumor-suppressing effects on CMM cells by inhibiting cell proliferation, cell cycle progression, migration, invasion, and induction of cell apoptosis.
Moreover, IL-24 had marked effects on downregulating the expression of angiogenesis-related proteins vascular endothelial growth factor, cluster of differentiation (CD) 31, CD34, collagen IV and metastasis-related factors CD147, membrane type-1 matrix metalloproteinase (MMP), and MMP-2 and MMP-9 in transplanted tumors.
There is also a significant correlation between the expression levels of CXCR4-CXCL12 axis and metastasis-related genes (E-cadherin and MMP2) in tumor samples with advanced stages of metastasis.
The as-prepared CDGM NPs could accumulate into the tumor tissue with the enhanced permeability and retention (EPR) effect as well as the active tumor targeting ability from the MMP2 polypeptides.
The expressions of VEGF and MMP-2 in serum of CRC patients were correlated with the depth of tumor infiltration, Dukes' staging, CLM and lymph node metastasis (p<0.05).
Then the degradation of the GNPs triggered by tumor extracellular matrix metalloproteinase-2 (MMP2) led to the release of prodrug Dox-Lac (Mw 898 Da) to facilitate the tumor tissue penetration and cellular uptake.
Delivery of DATS also resulted in decreased expression of Trx-1 as the direct target, as well as expression of NF-κB and MMP2/9 in primary tumor and lung tissue.
Additional complexities were revealed as the recruitment of host macrophages by the tumor cells was found to be the source of the tumorMMP-2/-9 activity and it is evident that MMP-2/-9 from both host and tumor is required for maximum signal using RACPP imaging for detection.
Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator MMP-14 are known to play a key role in tumour angiogenesis and the growth of many cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of the brain.