Nucleotide receptors control IL-8/CXCL8 and MCP-1/CCL2 secretions as well as proliferation in human glioma cells

Braganhol, Elizandra; Kukulski, Filip; Lévesque, Sébastien A.; Fausther, Michel; Lavoie, Élise G.; Zanotto-Filho, Alfeu; Bergamin, Letícia Scussel; Pelletier, Julie; Bahrami, Fatemeh; Yebdri, Fethia Ben; Moreira, José Cláudio Fonseca; Battastini, Ana Maria Oliveira; Sévigny, Jean

doi:10.1016/j.bbadis.2014.10.014

Cited by 51 publications

(41 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar data were observed upon P2X7R activation on human glioma cells, which caused monocyte chemoattractant protein-1 and interleukin-8/chemokine (C-X-C motif) ligand 8 secretion in a P2X7-dependent manner (Braganhol et al, 2015), and P2X7R regulates C6 glioma cell mobility and tumor cell migration (Wei et al, 2008;Ryu et al, 2011;Braganhol et al, 2015). Regarding signal pathways activated in malignant brain tumors, P2X7R mediated the activation of extracellular signal-regulated protein kinases 1 and 2 in human 1321N1 astrocytoma cells via an increase in [Ca 21 ]i.…”

Section: The Ionotropic Atp-gated P2x7 Receptorsupporting

confidence: 73%

“…Additionally, emerging evidence attributes the role of TRP channels in the regulation of homeostasis, growth control, cell survival, and describes their promising implications in GBM therapy. Furthermore, P2X7R activation is linked with elevated expression of inflammation promoting factors, tumor cell migration (Wei et al, 2008;Ryu et al, 2011;Braganhol et al, 2015), an increase in intracellular mobilization of Ca 21 , and membrane depolarization in malignant gliomas. Further studies are required though to assess which other calcium channels are associated with the development and progression of malignant brain tumors, and the roles that these channels play in the process.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

View full text Add to dashboard Cite

Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calciumpermeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca 21 activity plays an important role in the regulation of cell proliferation, and Ca 21 signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca 21 by modulating the driving force for Ca 21 entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca 21 -influx and an indirect activator of voltage-gated Ca 21 -channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca 21 , and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.

show abstract

Section: The Ionotropic Atp-gated P2x7 Receptorsupporting

confidence: 73%

Section: Resultsmentioning

confidence: 99%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

View full text Add to dashboard Cite

show abstract

“…Knockdown of P2Y 6 R expression decreased LPS-induced CXCL8 release as well as spontaneous release of CXCL8, suggesting endogenous basal release of nucleotides. Since glioblastoma multiforme is one of the most aggressive brain tumors, these data suggest that P2Y 6 R and/or P2X7R antagonists may be suitable candidates for controlling glioma progression [146].…”

Section: Inflammatory Chemokines(c-c Motif) Ligandsmentioning

confidence: 97%

“…As for CXCL8, P2R activation controlled both basal and LPS-induced CCL2 secretion from human glioma cells. Both P2X7Rs and P2Y 6 Rs appeared to be involved [146]. In microglia, ATP induced messenger RNA (mRNA) expression and release of CCL2, CCL3, and CXCL2 mainly through activation of P2X7Rs [151][152][153].…”

Section: Inflammatory Chemokines(c-c Motif) Ligandsmentioning

confidence: 98%

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Zimmermann

2015

Purinergic Signalling

View full text Add to dashboard Cite

Extracellular nucleotides, and ATP in particular, are cellular signal substances involved in the control of numerous (patho)physiological mechanisms. They provoke nucleotide receptor-mediated mechanisms in select target cells. But nucleotides can considerably expand their range of action. They function as primary messengers in intercellular communication by stimulating the release of other extracellular messenger substances. These in turn activate additional cellular mechanisms through their own receptors. While this applies also to other extracellular messengers, its omnipresence in the vertebrate organism is an outstanding feature of nucleotide signaling. Intercellular messenger substances released by nucleotides include neurotransmitters, hormones, growth factors, a considerable variety of other proteins including enzymes, numerous cytokines, lipid mediators, nitric oxide, and reactive oxygen species. Moreover, nucleotides activate or co-activate growth factor receptors. In the case of hormone release, the initially paracrine or autocrine nucleotide-mediated signal spreads through to the entire organism. The examples highlighted in this commentary suggest that acting as ubiquitous triggers of intercellular messenger release is one of the major functional roles of extracellular nucleotides. While initiation of messenger release by nucleotides has been unraveled in many contexts, it may have been overlooked in others. It can be anticipated that additional nucleotide-driven messenger functions will be uncovered with relevance for both understanding physiology and development of therapy.

show abstract

“…The 89-gene signature consists of a number of hypoxia and inflammation-related genes such as AKR1C3 [44], PTX3, PLAT [45] and IGFBP2 [46], showing that these two inseparable hallmarks are involved in tumor progression [47, 48] and play significant roles in glioma pathogenesis. Purinergic signaling related genes such as GPR17 [49], VEGFA [50] and CCL2 [51] are involved in inflammation leading to glioma growth [52, 53]. In addition, BCAT1 was reported to promote cell proliferation in gliomas carrying wild-type IDH1 [54].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value and their clinical implication of 89-gene signature in glioma

et al. 2016

View full text Add to dashboard Cite

Gliomas are the most common and aggressive primary tumors in adults. The current approaches, such as histological classification and molecular genetics, have limitation in prediction of individual therapeutic outcomes due to heterogeneity within the tumor groups. Recent studies have proposed several gene signatures to predict glioma's prognosis. However, most of the gene expression profiling studies have been performed on relatively small number of patients and combined probes from diverse microarray chips. Here, we identified prognostic 89 common genes from diverse microarray chips. The 89-gene signature classified patients into good and bad prognostic groups which differed in the overall survival significantly, reflecting the biological characteristics and heterogeneity. The robustness and accuracy of the gene signature as an independent prognostic factor was validated in three microarray and one RNA-seq data sets independently. By incorporating into histological classification and molecular marker, the 89-gene signature could further stratify patients with 1p/19q co-deletion and IDH1 mutation. Additionally, subset analyses suggested that the 89-gene signature could predict patients who would benefit from adjuvant chemotherapy. Conclusively, we propose that the 89-gene signature would have an independent and accurate prognostic value for clinical use. This study also offers opportunities for novel targeted treatment of individual patients.

show abstract

Nucleotide receptors control IL-8/CXCL8 and MCP-1/CCL2 secretions as well as proliferation in human glioma cells

Cited by 51 publications

References 61 publications

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Extracellular ATP and other nucleotides—ubiquitous triggers of intercellular messenger release

Prognostic value and their clinical implication of 89-gene signature in glioma

Contact Info

Product

Resources

About