Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias

Chong, Jing-Hui; Zheng, Guoguang; Zhu, Xiaofan; Guo, Ye; Wang, Lin; Ma, Chao; Liu, Shuyan; Xu, Lvjie; Yang, Lin; Wu, Ke‐Fu

doi:10.1016/j.bbrc.2009.11.087

Cited by 50 publications

(50 citation statements)

References 32 publications

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“…Finally, apoptosis was much less frequent in HEK293-hP2X7 than in HEK293-mock tumors, providing yet another sign of the more aggressive phenotype conferred by P2X7 transfection. Overall, these data are in keeping with previous reports linking increased P2X7 expression with poor prognosis in different leukemias (15,46) and solid tumors (18,19,36). Our findings were further strengthened by transfecting mP2X7 into the mouse colon cancer cell line CT26, and by generating CT26-mP2X7-derived tumors in syngeneic, immunocompetent BALB/c mice.…”

Section: Discussionsupporting

confidence: 92%

Expression of P2X7 Receptor IncreasesIn VivoTumor Growth

et al. 2012

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The P2X7 receptor is an ATP-gated ion channel known for its cytotoxic activity. However, recent evidence suggests a role for P2X7 in cell proliferation. Here, we found that P2X7 exhibits significant growth-promoting effects in vivo. Human embryonic kidney cells expressing P2X7 exhibited a more tumorigenic and anaplastic phenotype than control cells in vivo, and the growth rate and size of these tumors were significantly reduced by intratumoral injection of the P2X7 inhibitor-oxidized ATP. The accelerated growth of P2X7-expressing tumors was characterized by increased proliferation, reduced apoptosis, and a high level of activated transcription factor NFATc1. These tumors also showed a more developed vascular network than control tumors and secreted elevated amounts of VEGF. The growth and neoangiogenesis of P2X7-expressing tumors was blocked by intratumoral injection of the VEGF-blocking antibody Avastin (bevacizumab), pharmacologic P2X7 blockade, or P2X7 silencing in vivo. Immunohistochemistry revealed strong P2X7 positivity in several human cancers. Together, our findings provide direct evidence that P2X7 promotes tumor growth in vivo. Cancer Res; 72(12); 2957-69. Ó2012 AACR.

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Section: Discussionsupporting

confidence: 92%

Expression of P2X7 Receptor IncreasesIn VivoTumor Growth

et al. 2012

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“…In prostate cancer P2X7R expression was increased [33], and a monoclonal anti-P2X7R antibody is currently being designed for use as a prostate cancer biomarker. Similarly, in newly diagnosed pediatric acute leukemias P2X7R expression was increased, especially in cases of relapsed disease and the receptor was found to be fully functional [34]. In rat C6 glioma cells P2X7R mRNA and protein were upregulated upon exposure to P2X7R specific agonist BzATP, and the stimulation of P2X7R was linked to release of proinflammatory markers and tumour cell migration [35].…”

Section: Discussionmentioning

confidence: 99%

P2X7 receptors are a potential novel target for anti-glioma therapies

et al. 2014

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“…It has been claimed that the P2X7 receptor-mediated cytotoxic effects on KGla and J6-1 leukaemia cell lines may occur independently of the calcium response [468]. In paediatric acute leukaemia, RT-PCR and Western blots showed that P2X1, P2X4, P2X5 and P2X7 receptors were upregulated, while P2X2, P2X3 and P2X6 receptors were absent or marginally expressed and the highest expression of P2X7 receptors was found in relapsed patients [469]. They also showed a significant decrease in the expression of P2X4, P2X5 and P2X7 receptors after complete remission after chemotherapy.…”

Section: Lymphocytic Leukaemiamentioning

confidence: 99%

Purinergic signalling and cancer

Burnstock

Virgilio

2013

Purinergic Signalling

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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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Abnormal expression of P2X family receptors in Chinese pediatric acute leukemias

Cited by 50 publications

References 32 publications

Expression of P2X7 Receptor IncreasesIn VivoTumor Growth

Expression of P2X7 Receptor IncreasesIn VivoTumor Growth

P2X7 receptors are a potential novel target for anti-glioma therapies

Purinergic signalling and cancer

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