Cartilage Oligomeric Matrix Protein Promotes Radiation Resistance in Non-Small Cell Lung Cancer In Vitro

Cartilage oligomeric matrix protein (COMP) is an extracellular matrix protein that has recently been associated with worse patient outcomes in breast, prostate, colorectal and hepatocellular cancers. This study aimed to determine whether COMP was also associated with increased progression and resistance to radiation in non-small cell lung cancer (NSCLC). The proliferation, migration, invasion and cell viability of wild-type and COMP overexpressing NSCLC cell lines were assessed when treated with exogenous COMP, with or without radiation. In addition, these cells were treated with inhibitors of downstream signaling intermediates of COMP. Proteomics were performed on the A549 cell line treated with COMP, radiation and inhibitors. NSCLC cells treated with COMP or overexpressing COMP had greater proliferation, migration, invasion and viability when irradiated compared to non-overexpressed cells treated with radiation alone, but this effect was reversed when treated with Src or PI3k inhibitors. The NCI-H1437 cell line exhibited a decrease in proliferation when treated with exogenous COMP, however COMP overexpression mitigated the radiation-induced reduction. Proteomics analyses indicate that COMP promotes oxidative phosphorylation and drug resistance pathways. Therefore, COMP overexpression and treatment with exogenous COMP appears to protect NSCLC cells against radiation in vitro, however treatment with inhibitors reverses COMP-mediated protection and progression.