title: The purine receptor P2X7R regulates the release of pro-inflammatory cytokines in human craniopharyngioma.
abstract: Craniopharyngiomas (CPs) are usually benign, non-metastasizing embryonic malformations originating from the sellar area. They are, however, locally invasive and generate adherent interfaces with the surrounding brain parenchyma. Previous studies have shown the tumor microenvironment is characterized by a local abundance of adenosine triphosphate (ATP), infiltration of leukocytes and elevated levels of pro-inflammatory cytokines that are thought to be responsible, at least in part, for the local invasion. Here, we examine whether ATP, via the P2X7R, participates in the regulation of cytokine expression in CPs. The expression of P2X7R and pro-inflammatory cytokines were measured at the RNA and protein levels both in tumor samples and in primary cultured tumor cells. Furthermore, cytokine modulation was measured after manipulating P2X7R in cultured tumor cells by siRNA-mediated knockdown, as well as pharmacologically by using selective agonists and antagonists. The following results were observed. A number of cytokines, in particular IL-6, IL-8 and MCP-1, were elevated in patient plasma, tumor tissue and cultured tumor cells. P2X7R was expressed in tumor tissue as well as in cultured tumor cells. RNA expression as measured in 48 resected tumors was positively correlated with the RNA levels of IL-6, IL-8 and MCP-1 in tumors. Furthermore, knockdown of P2X7R in primary tumor cultures reduced, and stimulation of P2XR7 by a specific agonist enhanced the expression of these cytokines. This latter stimulation involved a Ca2+-dependent mechanism and could be counteracted by the addition of an antagonist. In conclusion, the results suggest that P2X7R may promote IL-6, IL-8 and MCP-1 production and secretion and contribute to the invasion and adhesion of CPs to the surrounding tissue.
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.|Nanfang Neurosurgery Research InstitutionNanfang hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.|Nanfang Neurosurgery Research InstitutionNanfang hospital, Southern Medical University, Guangzhou, China.
authors.forename: Guang-Long
authors.initials: GL
authors.lastname: Huang
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Sheng-Ze
authors.initials: SZ
authors.lastname: Deng
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.|Nanfang Neurosurgery Research InstitutionNanfang hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Chao-Hu
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China qisongtaonfyy@126.com panjundu@hotmail.com.|Nanfang Neurosurgery Research InstitutionNanfang hospital, Southern Medical University, Guangzhou, China.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Qi
authors.affiliation: Department of NeurosurgeryNanfang Hospital, Southern Medical University, Guangzhou, China qisongtaonfyy@126.com panjundu@hotmail.com.|Nanfang Neurosurgery Research InstitutionNanfang hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Pan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D016207:Cytokines; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7
keywords: P2X7 receptor; craniopharyngioma; cytokine; pituitary