Targeting P2X<sub>7</sub> receptor inhibits the metastasis of murine P388D1 lymphoid neoplasm cells to lymph nodes

Ren, Shuo; Zhang, Yi; Wang, Yujing; Lui, Yuejian; Wei, Wei; Huang, Xiaohua; Mao, Wenjuan; Zuo, Yongchun

doi:10.1042/cbi20090428

Cited by 22 publications

(13 citation statements)

References 27 publications

(36 reference statements)

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“…18 Some researchers believe that environment changes, resulting from the P2X 7 receptors activation, also contribute to the increased migration of cells through regulating the release of some cytokines. 35 Stromal derived factor 1a (SDF-1a/ CXCL12)/CXCR4 has been extensively illustrated in the recruitment and homing of EPCs to contribute to neovascularization of tumor or ischemic tissue. [39][40][41] Besides, other subtypes of CXC chemokines, such as CXCL1 and CXCL2, also show their important roles in EPCs recruitment.…”

Section: Discussionmentioning

confidence: 99%

“…In central nervous system, ATP exposure induces proliferation of neural stem cells (NSC) through the PI3k-kinase-dependent P70S6 kinase signaling pathway. 34 In some different cancer types, upregulated expression of P2X 7 receptors in tumor cells is closely related to tumor growth, such as breast cancer, 20 lymphoid neoplasm, 35 bone-related cancers 36 and so on. The present data showed that activation of P2X 7 receptors in spleen-derived EPCs using BzATP, an analog of ATP, contributed to enhanced cells proliferation.…”

Section: Discussionmentioning

confidence: 99%

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The expression of P2X₇receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

Fang

Chen

Wang

et al. 2015

Cancer Biology & Therapy

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In order to use endothelial progenitor cells (EPCs) as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas, how to enhance proliferation and targeting ability of transplanted EPCs is a high priority. Here, we confirmed, for the first time, the expression of P2X 7 receptors in rat spleen-derived EPCs. Activation of P2X 7 receptors in EPCs by BzATP promoted cells proliferation and migration, rather than apoptosis. In vivo, the homing of transplanted EPCs after long-term suppression of P2X 7 receptors by persistent BBG stimulation was evaluated by MRI, immunohistochemistry and flow cytometry. Compared to the group without BBG treatment, less transplanted EPCs homed to gliomas in the group with BBG treatment, especially integrated into the vessels containing tumor-derived endothelial cells in gliomas. Moreover, western blot showed that CXCL1 expression was downregulated in gliomas with BBG treatment, which meant P2X 7 receptors suppression inhibited the homing of EPCs to gliomas through downregulation of CXCLl expression. Further, effects of P2X 7 receptors on C6 glioma cells or gliomas were evaluated at the same dose of BzATP or BBG used in EPCs experiments in vitro and in vivo. MTT assay and MRI revealed that P2X 7 receptors exerted no significant promoting effect on C6 glioma cells proliferation, gliomas growth and angiogenesis. Taken together, our findings imply the possibility of promoting proliferation and targeting ability of transplanted EPCs to brain gliomas in vivo through P2X 7 receptors, which may provide new perspectives on application of EPCs as a therapeutic and imaging probe to overcome antiangiogenic resistance for gliomas.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The expression of P2X₇receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

Fang

Chen

Wang

et al. 2015

Cancer Biology & Therapy

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“…Alternatively, P2X7 activation may promote ATP-induced tumour cell survival and growth [7,8]. P2X7 activation may also facilitate tumour invasiveness and metastases [9] by inducing the release of matrix membrane metalloproteases [10] and cysteine cathepsins [11], and the shedding of cell adhesion molecules [12,13]. Despite these findings however, the role of P2X7 in neoplasia remains poorly defined.…”

Section: Introductionmentioning

confidence: 99%

P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells

Gadeock

Pupovac

Sluyter

et al. 2012

Purinergic Signalling

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The P2X7 purinergic receptor is an ATP-gated cation channel with an emerging role in neoplasia. In this study we demonstrate that the human KG-1 cell line, a model of acute myelogenous leukaemia, expresses functional P2X7. RT-PCR and immunochemical techniques demonstrated the presence of P2X7 mRNA and protein respectively in KG-l cells, as well as in positive control multiple myeloma RPMI 8226 cells. Flow cytometric measurements demonstrated that ATP induced ethidium(+) uptake into KG-l cells suspended in sucrose medium (EC(50) of ≈ 3 μM), but not into cells in NaCl medium. In contrast, ATP induced ethidium(+) uptake into RPMI 8226 cells suspended in either sucrose or NaCl medium (EC(50) of ≈ 3 or ≈ 99 μM, respectively), as well as into RPMI 8226 cells in KCl medium (EC(50) of ≈ 18 μM). BzATP and to a lesser extent ATPγS and αβ-methylene ATP, but not ADP or UTP, also induced ethidium(+) uptake into KG-1 cells. ATP-induced ethidium(+) uptake was completely impaired by the P2X7 antagonists, AZ10606120 and A-438079. ATP-induced ethidium(+) uptake was also impaired by probenecid but not by carbenoxolone, both pannexin-1 antagonists. ATP induced YO-PRO-1(2+) and propidium(2+) uptake into KG-1 cells. Finally, sequencing of full-length P2X7 cDNA identified several single nucleotide polymorphisms (SNPs) in KG-1 cells including H155Y, A348T, T357S and Q460R. RPMI 8226 cells contained A348T, A433V and H521Q SNPs. In conclusion, the KG-1 cell line expresses functional P2X7. This cell line may help elucidate the signalling pathways involved in P2X7-induced survival and invasiveness of myeloid leukaemic cells.

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“…Anaplastic large cell lymphomas are a distinct subset of non-Hodgkin's lymphomas and multikinase inhibitors have been recommended for the treatment of these tumours [486]. Inhibition of the expression and function of P2X7 receptors attenuated the metastatic capability of murine P388D1 lymphoid neoplasm cells [487]. Activation of P2X7 receptors caused depletion of intracellular ATP in T lymphoma cells [488].…”

Section: Lymphomasmentioning

confidence: 99%

Purinergic signalling and cancer

Burnstock

Virgilio

2013

Purinergic Signalling

262

265

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Receptors for extracellular nucleotides are widely expressed by mammalian cells. They mediate a large array of responses ranging from growth stimulation to apoptosis, from chemotaxis to cell differentiation and from nociception to cytokine release, as well as neurotransmission. Pharma industry is involved in the development and clinical testing of drugs selectively targeting the different P1 nucleoside and P2 nucleotide receptor subtypes. As described in detail in the present review, P2 receptors are expressed by all tumours, in some cases to a very high level. Activation or inhibition of selected P2 receptor subtypes brings about cancer cell death or growth inhibition. The field has been largely neglected by current research in oncology, yet the evidence presented in this review, most of which is based on in vitro studies, although with a limited amount from in vivo experiments and human studies, warrants further efforts to explore the therapeutic potential of purinoceptor targeting in cancer.

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Targeting P2X₇ receptor inhibits the metastasis of murine P388D1 lymphoid neoplasm cells to lymph nodes

Cited by 22 publications

References 27 publications

The expression of P2X₇receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

The expression of P2X₇receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells

Purinergic signalling and cancer

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Targeting P2X7 receptor inhibits the metastasis of murine P388D1 lymphoid neoplasm cells to lymph nodes

Cited by 22 publications

References 27 publications

The expression of P2X7receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

The expression of P2X7receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

P2X7 receptor activation mediates organic cation uptake into human myeloid leukaemic KG-1 cells

Purinergic signalling and cancer

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Product

Resources

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Targeting P2X₇ receptor inhibits the metastasis of murine P388D1 lymphoid neoplasm cells to lymph nodes

The expression of P2X₇receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas

The expression of P2X₇receptors in EPCs and their potential role in the targeting of EPCs to brain gliomas