摘要
PAF(PAFR)脂质介质的受体是一种表达于多种细胞类型中的G-蛋白偶联的受体。除了PAF外,一系列的氧化磷脂也能与PAFR结合;。凋亡细胞同样也表达PAFR配体,在这两种情况下中,清除剂受体都有参与。有证据表明,该清除剂受体CD36和PAFR与巨噬细胞细胞膜和信号传导共同诱导调节表型产生的活动相关。在肿瘤微环境中,缺氧产生PAF样磷脂,使得凋亡细胞数量较多缺氧使凋亡细胞数量增多并产生类似PAF的磷脂。肿瘤巨噬细胞和树突状细胞各自表达的PAFR的接合诱导了调节或致耐受表型的产生并且、破坏了肿瘤先天性和适应性的免疫应答。在癌症治疗中,PAFR配体的产生,可以生成PAFR配体,进一步加重了免疫抑制。此外,某些肿瘤细胞可以通过在化疗过程中所产生的PAFR配体,来表达PAFR及其激活物,诱导抗凋亡因子。这些因子保护肿瘤细胞以防它们在这些诱导治疗中死亡。建议PAFR拮抗剂与化疗联合运用,可能成为一个有前景的癌症治疗策略。
关键词: 化疗,血小板活化因子受体,肿瘤生长,肿瘤的巨噬细胞,肿瘤微环境。
Current Drug Targets
Title:PAF Receptor and Tumor Growth
Volume: 15 Issue: 10
Author(s): Sonia Jancar and Roger Chammas
Affiliation:
关键词: 化疗,血小板活化因子受体,肿瘤生长,肿瘤的巨噬细胞,肿瘤微环境。
摘要: The receptor for the lipid mediator PAF (PAFR) is a G-protein coupled receptor expressed in several cell types. Besides PAF, a series of oxidized phospholipids can also bind to PAFR. Dying cells also express PAFR-ligands and, in both situations, scavenger receptors are involved as well. There is evidence that the scavenger receptor CD36 and PAFR associate in the macrophages membrane and signal in conjunction to induce a regulatory phenotype. In the tumor microenvironment, apoptotic cells are abundant due to hypoxia, and PAF-like phospholipids are generated. Engagement of PAFR expressed by tumor macrophages and dendritic cells induces a regulatory/tolerogenic phenotype and subverts the innate and adaptive immune response to the tumor. During cancer therapies, PAFR-ligands can be generated, further aggravating the immune suppression. Moreover, some tumor cells express PAFR and its activation by PAFR-ligands generated during chemotherapy induce anti-apoptotic factors, which protect the tumor cells from death induced by these treatments. It is proposed that PAFR antagonists, administered in combination with chemotherapy, may represent a promising strategy for cancer treatment.
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Cite this article as:
Jancar Sonia and Chammas Roger, PAF Receptor and Tumor Growth, Current Drug Targets 2014; 15 (10) . https://dx.doi.org/10.2174/1389450115666140903111812
DOI https://dx.doi.org/10.2174/1389450115666140903111812 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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