Matrix metalloproteinase (MMP) and immunosuppressive biomarker profiles of seven head and neck squamous cell carcinoma (HNSCC) cell lines

Abstract

Background: Biomarkers like programmed death ligand-1 (PDL1) have become a focal point for immunotherapeutic checkpoint inhibition in head and neck squamous cell carcinoma (HNSCC). However, it’s only part of the total immunosuppressive biomarker profile of HNSCC cells. Matrix metalloproteinases (MMPs) are enzymes that break down the basement membrane allowing cancer cells to metastasize and play an important role in the tumor microenvironment. MMPs can also activate certain cytokines, growth factors, and chemokines post-translationally. The objective of this study was to determine MMP and biomarker profiles of seven different HNSCC cell lines. Methods: Authenticated cell lines were grown in minimal media at 1×106 viable cells/mL and incubated at 37 °C. After 24 hrs supernatants were collected, and adhering cells were lysed. Multiplex immunoassays were used to determine MMP1, MMP7, MMP9, IL-6, VEGFA, IL-1α, TNF-α, GM-CSF, IL-1RA, and IL-8 concentrations in supernatants. ELISAs were used to determine PDL1, CD47, FASL, and IDO concentrations in cell lysates. A one-way ANOVA was fit to examine log-transformed concentrations of biomarkers between seven HNSCC cell lines, and pairwise group comparisons were conducted using post- hoc Tukey’s honest significance test (α=0.05). Results: Significant differences (P<0.05) in MMP and biomarker concentrations were found between the seven HNSCC cell lines. For example, MMP9 was highest in SCC25 and UM-SCC99, MMP7 was highest in SCC25 and UM-SCC19, and MMP1 was highest in SCC25. Conclusions: These results suggest different patients’ HNSCC cells can express distinct profiles of select biomarkers and MMPs, which could be due to metastatic stage of the cancer, primary tumor site, type of tissue the tumor originated from, or genomic differences between patients. MMP and biomarker expression profiles should be considered when choosing cell lines for future studies. The results support the reason for personalized medicine and the need to further investigate how it can be used to treat HNSCC.

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib

“…In HNSCC, different results on IDO1 are documented, and expression is heterogeneous among different HNSCC cell lines. Of note, IDO1 abundance of primary resection specimen and cultured cells seems to be independent from anatomical site and HPV status (40). Still, IDO1 is a useful marker for progression of in oral squamous cell carcinoma (41).…”

“…Indirect effects of TRP metabolism include interference with other biological functions like migration, angiogenesis, and cell growth regulation (18,40). To investigate the influence of anticancer drugs on TRP catabolism, we performed a comprehensive analysis using conventional chemotherapy (TMZ, 5-FU, Cisplatin, Gemcitabine) and targeted drugs (Cetuximab, Dinaciclib).…”

HBD3 Induces PD-L1 Expression on Head and Neck Squamous Cell Carcinoma Cell Lines

“…Bates et al found that PD-L1 was present in differing concentrations on the surface of HNSCC cell lines in Table 1 by ELISA, and we summarized this information in Table 2 [10]. PD-L1 concentrations in cell lysates ranged from 79.67 to 539.79 pg/mL.…”

“…HNSCCs arise through the accumulation of genetic and epigenetic changes in genes acting in cancer-associated signaling pathways [1,7,8]. HNSCC cells produce a variety of immunosuppressive cytokines, chemokines, and biomarkers [9,10]. Among these is programmed death-ligand 1 (PD-L1) [10].…”

“…HNSCC cells produce a variety of immunosuppressive cytokines, chemokines, and biomarkers [9,10]. Among these is programmed death-ligand 1 (PD-L1) [10].…”