Inhibition of matrix metalloproteinase‐2 modulates malignant behaviour of oral squamous cell carcinoma cells

Abstract

Background Matrix metalloproteinases (MMPs) play a crucial role in the malignant phenotype of cancer cells. In particular, active levels of MMP2 in cancer cells have been associated with invasion and metastasis through the degradation of basement membrane extracellular matrix proteins. However, little is known about the role of this potential biomarker in oral cancer. Our aim was to investigate the effect of MMP2 inhibition on OSCC activity in vitro, as well as to assess MMP2 dysregulation in oral cancer samples. Methods Human OSCC cell lines H357 and H400 were tested with the selective MMP2 inhibitor ARP101 and the MMP2 neutralising monoclonal antibody MA5‐13590 to assess cell proliferation in vitro using MTS assay. Cell migration at 12/24 h was assessed using a Transwell migration assay. Cell invasion was assessed at 24 h using a Corning Matrigel invasion assay. MMP2 expression was assessed in 208 tissue samples (related to 60 OSCC cases and nine normal control) using tissue microarray (TMA) and further analysed via TCGA. Results Both ARP101 and MA5‐13590 monoclonal antibody reduced cell proliferation in both the cell lines tested. Treatment with 4μg/mL of MMP2 monoclonal antibody showed a significant decrease in cell migration at 24 hours. The administration of ARP101 and monoclonal antibody to H357 and H400 cell lines induced a drastic reduction in cell invasion at 24 h compared to the control. In patients, TCGA analysis demonstrated that oral cancer tissues express significantly higher levels of MMP2 mRNA compared to normal oral tissues. Further, IHC analysis on TMA showed significant difference in MMP2 protein expression between low and high histopathological grade OSCC. Conclusions We have demonstrated, for the first time, that MMP2 inhibition affects oral cancer cells ability to survive, migrate and invade in vitro. Differences between MMP2 expression in normal and malignant tissues varied. Further research on the role of MMP2 in OSCC and novel mechanisms to inhibit MMP2‐dependent pathways should be encouraged.

Combination of β2-AR Blocker and COX-2 Inhibitor Suppresses Development of Oral Squamous Cell Carcinoma

“…The protein expression level of these above four genes were also the lowest in the four groups in vitro and vivo. EGFR, TGF-β1, IL-1β and MMP2 were all related to invasion and metastasis of malignant tumors, including OSCC [36][37][38][39][40][41]. So, we have veri ed that combined use of ICI118,551 and etodolac can inhibit the development of OSCC and the expression of EGFR, TGF-β1, IL-1β and MMP2 indeed.…”

Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro

“…The OSCC cell lines were cultured as previously described 41 . Cell lines were cultured in 100-mm Petri plastic dishes (Corning 430167) and grown to 60%-80% confluence before being further sub-cultured.…”

“…Epithelial cells grown to 80% confluency were subsequently detached via a pre-treatment of 10 mM EDTA for 10 min, followed subsequently with incubation with a 0.25% trypsin in 1 mM EDTA solution (T4049, Sigma-Aldrich, Castle Hill, NSW, Australia) for 5 min. The viability of the keratinocytes was confirmed by trypan blue exclusion (trypan blue dye, 0.4% solution, 1450021, Bio-Rad) 41 .…”

“…Migration assay. In vitro cell migration of H400 and BICR56 cells was assessed at 16 h using a Transwell migration assay (CLS3422, Sigma-Aldrich) as previously described 41 . Kava constituents FKA (10 μg/ml), FKB (2.5 μg/ml) and yangonin (10 μg/ml) were used to treat the cells in the upper chambers of the assay.…”

Expression of Ubiquitin-specific protease 7 in oral squamous cell carcinoma promotes tumor cell proliferation and invasion

“…OSCC patients with high Ki-67 expression showed a significantly increased risk of poor overall survival as well as disease-free survival (Jing et al, 2018). In addition, invasion-metastasis-related factor matrix metalloproteinase 2 (MMP2) was shown to improve OSCC migration and invasion (Celentano et al, 2021); Angiogenesis was also involved in OSCC progression. Vascular endothelial growth factor (VEGF) and its receptor VEGFR are the main factors that are responsible for angiogenesis (Mărgăritescu et al, 2009).…”