Cho Hee Jin, Yeo Dong Jun, Yang HeeWoong, Koo JaeHyung
Department of Biomedical Convergence Science and Technology, Advanced Institute of Science and Technology, Kyungpook National University, Daegu 41566, Republic of Korea.
Cell and Matrix Research Institute, Kyungpook National University, Daegu 41944, Republic of Korea.
Int J Mol Sci. 2024 Dec 13;25(24):13382. doi: 10.3390/ijms252413382.
Odorant receptors (ORs), which constitute approximately 50% of all human G protein-coupled receptors, are increasingly recognized for their diverse roles beyond odor perception, including functions in various pathological conditions like brain diseases and cancers. However, the roles of ORs in glioblastoma (GBM), the most aggressive primary brain tumor with a median survival of only 15 months, remain largely unexplored. Here, we performed an integrated transcriptomic analysis combining The Cancer Genome Atlas RNA-seq and single-cell RNA sequencing data from GBM patients to uncover cell-type-specific roles of ORs within the tumor and its microenvironment. Our findings reveal that ORs display distinct expression patterns, with enriched in pericytes linked to vascular remodeling and angiogenesis, OR2B11 associated with tumor-associated macrophages supporting immunosuppressive phenotypes, and OR2L13 correlated with synaptic activity in recurrent tumors, potentially mediating treatment-induced neuronal adaptations. These results highlight ORs as potential therapeutic targets, offering new insights into their regulatory roles in GBM progression, immune modulation, and treatment resistance.
气味受体（ORs）约占人类所有G蛋白偶联受体的50%，其在气味感知之外的多种作用日益受到认可，包括在脑疾病和癌症等各种病理状况中的功能。然而，ORs在胶质母细胞瘤（GBM）中的作用在很大程度上仍未得到探索，GBM是最具侵袭性的原发性脑肿瘤，中位生存期仅为15个月。在此，我们结合癌症基因组图谱RNA测序和来自GBM患者的单细胞RNA测序数据进行了综合转录组分析，以揭示ORs在肿瘤及其微环境中的细胞类型特异性作用。我们的研究结果表明，ORs呈现出不同的表达模式，其中 在与血管重塑和血管生成相关的周细胞中富集，OR2B11与支持免疫抑制表型的肿瘤相关巨噬细胞相关，OR2L13与复发性肿瘤中的突触活动相关，可能介导治疗诱导的神经元适应性变化。这些结果突出了ORs作为潜在治疗靶点的地位，为其在GBM进展、免疫调节和治疗抗性中的调控作用提供了新的见解。
