Expression of P2X7 in human hematopoietic cell lines and leukemia patients

Zhang, Xiujun; Zheng, Guoguang; Ma, Xiaotong; Yang, Yue; Li, Ge; Rao, Qing; Nie, Kun; Wu, Ke‐Fu

doi:10.1016/j.leukres.2004.04.001

Cited by 86 publications

(72 citation statements)

References 37 publications

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“…Several tumors have been shown to express P2X 7 at unusually high levels (13,(34)(35)(36)(37)(38). In some cases (i.e., breast and prostate cancer), it was suggested that the P2X 7 might be nonfunctional (36,37), but no data were presented to support this claim.…”

Section: Discussionmentioning

confidence: 99%

The P2X7 Receptor Sustains the Growth of Human Neuroblastoma Cells through a Substance P–Dependent Mechanism

et al. 2006

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P2X 7 is a receptor for extracellular nucleotides expressed by different normal cell types. P2X 7 triggering may result in stimulation of cell proliferation or induction of apoptosis depending on the level of activation. P2X 7 expression and function in B-cell chronic lymphocytic leukemia has been shown to correlate with disease severity. Here, we have asked the question of whether P2X 7 is expressed and functional in neuroblastoma, a pediatric tumor of neuroectodermal origin. P2X 7 was detected both in primary neuroblastoma tumors and in neuroblastoma cell lines. In the latter cells, P2X 7 stimulation by ATP was found to trigger (a) increased intracellular calcium fluxes, (b) plasma membrane depolarization, and (c) formation of a nonselective plasma membrane permeable pore. In contrast to the usual response typically observed in the majority of cell types, P2X 7 in vitro stimulation did not induce caspase-3 activation or apoptosis of neuroblastoma cells but rather supported their proliferation. Growth stimulation was partially due to substance P release from nucleotide-activated neuroblastoma cells. Therefore, neuroblastoma cells seem to have molded P2X 7 function to their advantage in two ways (i.e., by silencing P2X 7 proapoptotic activity and by coupling P2X 7 stimulation to release of locally acting trophic factors). (Cancer Res 2006; 66(2): 907-14)

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Section: Discussionmentioning

confidence: 99%

The P2X7 Receptor Sustains the Growth of Human Neuroblastoma Cells through a Substance P–Dependent Mechanism

et al. 2006

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“…␤-Cell chronic lymphocyte leukemia is unique in showing a 3-fold increased incidence in closely related family members compared with other lymphoproliferative diseases; a candidate gene for this familial incidence is the P2X 7 gene (Dao-Ung et al, 2004). Expression of P2X 7 receptor mRNA is higher in most types of leukemia, although there is loss of P2X 7 receptor function (Zhang et al, 2004c).…”

Section: Oncologymentioning

confidence: 99%

Pathophysiology and Therapeutic Potential of Purinergic Signaling

2006

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“…Among the members of the P2X receptors family, the latest cloned P2X 7 receptors (P2X 7 R) (Rassendren et al, 1997) are very unique by different features, some of them are: (1) their sensitivity to ATP (North, 2002), (2) their facilitation under successive or sustained applications of agonist (Hibell et al, 2000;Roger et al, 2008Roger et al, , 2010a and (3) the appearance of a large, non-selective membrane pore after sustained stimulations with ATP (Pelegrin and Surprenant, 2006). Recently, several tumours have been shown to express P2X 7 R at unusually high levels (Adinolfi et al, 2002;Zhang et al, 2004;Slater et al, 2004a, b;Wang et al, 2004a;Raffaghello et al, 2006;Deli et al, 2007;Solini et al, 2008), however, their functionality and involvement in the physiology of cancer cells remain unclear. In some studies performed on breast and prostate cancers, it was suggested that P2X 7 R might be non-functional (Slater et al, 2004a, b), but proposed to serve as an early marker for cancer (Slater et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness

et al. 2011

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ATP-gated P2X 7 receptors (P2X 7 R) are unusual plasma membrane ion channels that have been extensively studied in immune cells. More recently, P2X 7 R have been described as potential cancer cell biomarkers. However, mechanistic links between P2X 7 R and cancer cell processes are unknown. Here, we show, in the highly aggressive human breast cancer cell line MDA-MB-435s, that P2X 7 receptor is highly expressed and fully functional. Its activation is responsible for the extension of neurite-like cellular prolongations, of the increase in cell migration by 35% and in cell invasion through extracellular matrix by 150%. The change in cancer cell morphology and the increased migration appeared to be due to the activation of Ca 2 þ -activated SK3 potassium channels. The enhanced invasion through the extracellular matrix was related to the increase of mature forms of cysteine cathepsins in the extracellular medium, which was independent of SK3 channel activity and not associated with cell death. Pharmacological targeting of P2X 7 R in vivo was crucial for cell invasiveness in a zebrafish model of metastases. Our results demonstrate a novel mechanistic link between P2X 7 R functionality in cancer cells and invasiveness, a key parameter in tumour growth and in the development of metastases. They also suggest a potential therapeutic role for the newly developed P2X 7 R antagonists.

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Expression of P2X7 in human hematopoietic cell lines and leukemia patients

Cited by 86 publications

References 37 publications

The P2X7 Receptor Sustains the Growth of Human Neuroblastoma Cells through a Substance P–Dependent Mechanism

The P2X7 Receptor Sustains the Growth of Human Neuroblastoma Cells through a Substance P–Dependent Mechanism

Pathophysiology and Therapeutic Potential of Purinergic Signaling

P2X7 receptor activation enhances SK3 channels- and cystein cathepsin-dependent cancer cells invasiveness

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