Insel Paul A, Sriram Krishna, Salmerón Cristina, Wiley Shu Z
Departments of Pharmacology, University of California, San Diego, CA 92093, USA.
Departments of Medicine, University of California, San Diego, CA 92093, USA.
Future Med Chem. 2020 Mar;12(6):523-532. doi: 10.4155/fmc-2019-0357. Epub 2020 Mar 2.
Cells in tumor microenvironments (TMEs) use several mechanisms to sense their low pH (<7.0), including via proton-sensing G protein-coupled receptors (psGPCRs): GPR4, GPR65/TDAG8, GPR68/OGR1 and GPR132/G2A. Numerous cancers have increased expression of psGPCRs. The psGPCRs may contribute to features of the malignant phenotype via actions on specific cell-types in the TME and thereby promote tumor survival and growth. Here, we review data regarding psGPCR expression in tumors and cancer cells, impact of psGPCRs on survival in solid tumors and a bioinformatics approach to infer psGPCR expression in cell types in the TME. New tools are needed to help define contributions of psGPCRs in tumor biology and to identify potentially novel therapeutic agents for a variety of cancers.
肿瘤微环境（TMEs）中的细胞通过多种机制感知其低pH值（<7.0），包括通过质子感应G蛋白偶联受体（psGPCRs）：GPR4、GPR65/TDAG8、GPR68/OGR1和GPR132/G2A。许多癌症中psGPCRs的表达增加。psGPCRs可能通过对TME中特定细胞类型的作用，促成恶性表型的特征，从而促进肿瘤的存活和生长。在此，我们综述了有关psGPCRs在肿瘤和癌细胞中的表达数据、psGPCRs对实体瘤存活的影响以及一种推断TME中细胞类型psGPCRs表达的生物信息学方法。需要新的工具来帮助确定psGPCRs在肿瘤生物学中的作用，并为多种癌症识别潜在的新型治疗药物。
