IADR Abstract Archives
Functional expression of class B scavenger receptors by oral keratinocytes: implications for oral squamous cell carcinoma
Objectives: Scavenger receptors (SR) belong to a large receptor family that primarily bind lipid-containing molecules. Until recently their expression has been described on innate immune cells (macrophages) and endothelial cells where their principal role is internalization of lipoproteins and bacteria. This study aimed to determine functional expression of Class B SR by oral keratinocytes.
Methods: A panel of normal, dysplastic or cancerous oral keratinocytes from various oral sites were tested for the expression of class B SR by qPCR, flow cytometry and immunohistochemistry. Oxidised (Ox) or acetylated (Ac) low-density lipoprotein (LDL) internalization was measured by immunofluorescence microscopy and receptor activation by immunoblotting for several intracellular signaling molecules. The effects of Ox/Ac-LDL on cell adhesion, invasion and migration as well as markers for epithelial to mesenchymal transition (EMT) were also measured in vitro.
Results: Class B SR family members were expressed by both normal and oral cancer cells with some cancer cells expressing elevated levels. Expression was markedly greater in oral cancer tissue than in normal oral mucosa. SCC4 cancer cells rapidly internalized Ox/Ac-LDL in a receptor-dependent manner that initiated phosphorylation of JNK. Stimulation with Ac, and in particular, Ox-LDL caused SCC4 cells to be less adherent, more invasive and display increased migration compared to controls. These cell functions were inhibited using a pan-Class B antagonist or a JNK inhibitor. In addition, Ox-LDL altered the expression of EMT markers.
Conclusions: These data suggest that Class B SR are up-regulated by oral cancer cells and that their activation by Ox-LDL may significantly impact on their ability to migrate and metastasise. Our findings may have a significant impact on oral cancer biology.
Methods: A panel of normal, dysplastic or cancerous oral keratinocytes from various oral sites were tested for the expression of class B SR by qPCR, flow cytometry and immunohistochemistry. Oxidised (Ox) or acetylated (Ac) low-density lipoprotein (LDL) internalization was measured by immunofluorescence microscopy and receptor activation by immunoblotting for several intracellular signaling molecules. The effects of Ox/Ac-LDL on cell adhesion, invasion and migration as well as markers for epithelial to mesenchymal transition (EMT) were also measured in vitro.
Results: Class B SR family members were expressed by both normal and oral cancer cells with some cancer cells expressing elevated levels. Expression was markedly greater in oral cancer tissue than in normal oral mucosa. SCC4 cancer cells rapidly internalized Ox/Ac-LDL in a receptor-dependent manner that initiated phosphorylation of JNK. Stimulation with Ac, and in particular, Ox-LDL caused SCC4 cells to be less adherent, more invasive and display increased migration compared to controls. These cell functions were inhibited using a pan-Class B antagonist or a JNK inhibitor. In addition, Ox-LDL altered the expression of EMT markers.
Conclusions: These data suggest that Class B SR are up-regulated by oral cancer cells and that their activation by Ox-LDL may significantly impact on their ability to migrate and metastasise. Our findings may have a significant impact on oral cancer biology.