Increased P2X7 Receptor Expression and Function in Thyroid Papillary Cancer: A New Potential Marker of the Disease?

Solini, Anna; Cuccato, Sabina; Ferrari, Davide; Santini, Eleonora; Gulinelli, Sara; Callegari, Maria Giulia; Dardano, Angela; Faviana, Pinuccia; Madec, Stéphanie; Virgilio, Francesco Di; Monzani, Fabio

doi:10.1210/en.2007-1223

Cited by 123 publications

(109 citation statements)

References 31 publications

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“…Surprisingly, it was found that P2X 7 R is expressed at very high levels in several tumours, compared with Deli et al, 2007;Solini et al, 2008) and was even proposed to represent an early cancer marker (Slater et al, 2005). In fact, among all cancer types tested, cervical cancer is the only exception to our knowledge with a decreased expression of P2X 7 R in cancer cells (Li et al, 2006).…”

Section: Discussionmentioning

confidence: 94%

“…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%

“…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). In other cancers, P2X 7 R activity could be responsible for anti-apoptotic effects (Deli et al, 2007), for sustaining cell growth (Raffaghello et al, 2006) or for the release of IL-6 by cancer cells (Solini et al, 2008). On the contrary, it was proposed to induce apoptosis in normal cervical epithelial cells (Wang et al, 2004a) and that its expression was decreased in cervical cancers (Li et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…First, it can be an anti‐tumour receptor inducing cancer cell death 16, 17. Second, P2X7R can also be a procancer receptor, as it supports cancer cell proliferation, migration and invasion, both in vitro 18, 19 and in vivo 20. One explanation is that these seemingly opposite effects depend on expression/interaction of presumed proapoptotic P2X7A isoform and trophic isoform P2X7B 21.…”

Section: Introductionmentioning

confidence: 99%

Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

Giannuzzo

Saccomano

Napp

et al. 2016

Intl Journal of Cancer

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The ATP‐gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu‐1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive, further affected cell survival and confirmed complex functionality of P2X7R. PancTu‐1 Luc migration and invasion was reduced by AZ10606120, and it was stimulated by PSCs, but not by PSCs from P2X7‐/‐ animals. PancTu‐1 Luc cells were orthotopically transplanted into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120‐treated mice showed reduced bioluminescence compared to saline‐treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct structures. PSCs number/activity and collagen deposition was reduced in AZ10606120‐treated tumours.

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“…P2 receptors are also expressed in many types of cancer [9]. Among these molecules, P2X7 receptor shows increased expression in many types of cancer cells [10][11][12][13][14]. Furthermore, activation of P2X7 receptor has been implicated in tumor growth, as well as tumor angiogenesis and metastasis of breast cancer [6, 10-12, 15, 16].…”

Section: Introductionmentioning

confidence: 99%

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

Takai

Tsukimoto

Hishida

et al. 2014

Purinergic Signalling

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Extracellular nucleotides, such as ATP, are released from cells and play roles in various physiological and pathological processes through activation of P2 receptors. Here, we show that autocrine signaling through release of ATP and activation of P2X7 receptor influences migration of human lung cancer cells. Release of ATP was induced by stimulation with TGF-β1, which is a potent inducer of cell migration, in human lung cancer H292 cells, but not in noncancerous BEAS-2B cells. Treatment of H292 cells with a specific antagonist of P2X7 receptor resulted in suppression of TGF-β1-induced migration. PC-9 human lung cancer cells released a large amount of ATP under standard cell culture conditions, and P2X7 receptor-dependent dye uptake was observed even in the absence of exogenous ligand, suggesting constitutive activation of P2X7 receptor in this cell line. PC-9 cells showed high motile activity, which was inhibited by treatment with ecto-nucleotidase and P2X7 receptor antagonists, whereas a P2X7 receptor agonist enhanced migration. PC-9 cells also harbor a constitutively active mutation in epidermal growth factor receptor (EGFR). Treatment with EGFR tyrosine kinase inhibitor AG1478 suppressed both cell migration and P2X7 receptor expression in PC-9 cells. Compared to control PC-9 cells, cells treated with P2X7 antagonist exhibited broadened lamellipodia around the cell periphery, while AG1478-treated cells lacked lamellipodia. These results indicate that P2X7-mediated signaling and EGFR signaling may regulate migration of PC-9 cells through distinct mechanisms. We propose that autocrine ATP-P2X7 signaling is involved in migration of human lung cancer cells through regulation of actin cytoskeleton rearrangement.

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Increased P2X7 Receptor Expression and Function in Thyroid Papillary Cancer: A New Potential Marker of the Disease?

Cited by 123 publications

References 31 publications

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

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

Targeting of the P2X7 receptor in pancreatic cancer and stellate cells

Autocrine signaling via release of ATP and activation of P2X7 receptor influences motile activity of human lung cancer cells

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