Title: Novel Molecues Inhibit Matrix Metalloproteinases in Squamous Cell Carcinoma Model
Thomas Bordieri (Presenter)
Roseman University of Health Sciences
Andrew Gross, Roseman University of Health Sciences
Catalina Matias, Roseman University of Health Sciences
Objectives: Squamous cell carcinomas (SCCs) are the most common of all head and neck oral cancer. SCC cells are recognized to express Matrix Metalloproteinases (MMPs), known to contribute to invasive metastasis. MMPs -2, -9, -13 are well recognized as contributing factors to tissue destruction in SCC metastasis. We propose that a family of novel small molecule inhibitors may limit the metastatic processes in the context of SCC, showing high affinity for targets known to propagate MMPs -2, -9, and -13.
Methods: Cal-27 cells acquired from ATCC along with antibodies specific for MMP -2, -3, -9, -13, MT1-MMP, Stat3, and pStat3. Cells incubated with varying small molecules at differing concentrations help evaluate MMP upregulation and STAT3 phosphorylation. Additionally, expansion assays were performed on Matrigel matrix to assess Cal-27 invasiveness post incubation with small molecules.
Results: 24hr incubation with compound C-b22 significantly reduced protein expression of MMPs-2, -9 and -13 in Cal-27 cells (p<0.001). Significant decrease in Stat3 phosphorylation is also observed (p<001). Cellular invasiveness is limited to 23% of control as observed in Matrigel expansion assays in a dose dependent manner (P<0.0001, one-way ANOVA).
Conclusions: Novel small molecules may present as promising therapeutics in reducing the expression of MMPs known to propagate cellular invasiveness of the squamous cell carcinoma line, Cal-27. While early recognition of premalignant and malignant lesions is essential to improving prognosis, controlling the expression of molecules responsible for metastasis may offer as therapeutic adjuncts for the treatment of oral squamous cell carcinoma.