Reno Kaitlyn E, Costa-Terryll Alicia, Park Sun H, Hughes Ryan T, Farris Michael K, Xing Fei, Willey Jeffrey S
Department of Radiation Oncology, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston Salem, NC 27157, USA.
Department of Cancer Biology, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston Salem, NC 27157, USA.
Int J Mol Sci. 2025 Mar 10;26(6):2465. doi: 10.3390/ijms26062465.
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.
软骨寡聚基质蛋白（COMP）是一种细胞外基质蛋白，最近发现它与乳腺癌、前列腺癌、结直肠癌和肝细胞癌患者的不良预后有关。本研究旨在确定COMP是否也与非小细胞肺癌（NSCLC）的进展增加和对放疗的抗性有关。在用或不用放疗的情况下，用外源性COMP处理野生型和COMP过表达的NSCLC细胞系，评估其增殖、迁移、侵袭和细胞活力。此外，用COMP下游信号中间体的抑制剂处理这些细胞。对用COMP、放疗和抑制剂处理的A549细胞系进行蛋白质组学分析。与单独接受放疗的未过表达细胞相比，用COMP处理或过表达COMP的NSCLC细胞在接受放疗时具有更强的增殖、迁移、侵袭和活力，但在用Src或PI3k抑制剂处理时，这种效应会逆转。用外源性COMP处理时，NCI-H1437细胞系的增殖减少，然而COMP过表达减轻了辐射诱导的增殖减少。蛋白质组学分析表明，COMP促进氧化磷酸化和耐药途径。因此，COMP过表达和用外源性COMP处理似乎在体外保护NSCLC细胞免受辐射，然而用抑制剂处理可逆转COMP介导的保护和进展。
