Expression of the Purinergic P2X7 Receptor in Murine MOPC315.BM Myeloma Cells
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Expression of the Purinergic P2X7 Receptor in Murine MOPC315.BM Myeloma Cells. / Risborg Høyer, Eva; Demir, Melisa ; Bak, Lasse Kristoffer; Jørgensen, Niklas Rye; Agrawal, Ankita.
In: Receptors, Vol. 2, No. 3, 2023, p. 191-203.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Expression of the Purinergic P2X7 Receptor in Murine MOPC315.BM Myeloma Cells
AU - Risborg Høyer, Eva
AU - Demir, Melisa
AU - Bak, Lasse Kristoffer
AU - Jørgensen, Niklas Rye
AU - Agrawal, Ankita
PY - 2023
Y1 - 2023
N2 - The adenosine-5’ triphosphate (ATP)-gated, ion channel, P2X receptor superfamily has seven members expressed by many cancer types. Subtype 7 (P2X7 receptor) is expressed consistently at levels higher than in comparatively healthy tissues. Moreover, transcript variant heterogeneity is associated with drug resistance. We have previously described the role of the P2X7 receptor in myeloma, a rare blood disease that uniquely presents with aggressive bone destruction. In this study, we used known agonists of the P2X7 receptor to induce calcium influx and YO-PRO-1 uptake in murine MOPC315.BM myeloma cells as readouts of P2X7 receptor-mediated channel activation and pore formation, respectively. Neither ATP- nor BzATP-induced calcium influx and YO-PRO-1 indicated an absence of the P2X7 receptor function on MOPC315.BM cells. TaqMan revealed low (Ct > 35) P2rx7 but high P2rx4 gene expression in MOPC315.BM; the latter was downregulated with BzATP treatment. The concomitant downregulation of CD39/Entpd1, Icam-1, and Nf-kb1 and the upregulation of Casp-1 genes regulated during purinergic signaling and with established roles in myeloma progression suggest P2RX4-mediated survival adaptation by cancer cells. Further studies are needed to characterize the P2RX4 pharmacology on MOPC315.BM since transcriptional regulation may be utilized by cancer cells to overcome the otherwise toxic effects of high extracellular ATP.
AB - The adenosine-5’ triphosphate (ATP)-gated, ion channel, P2X receptor superfamily has seven members expressed by many cancer types. Subtype 7 (P2X7 receptor) is expressed consistently at levels higher than in comparatively healthy tissues. Moreover, transcript variant heterogeneity is associated with drug resistance. We have previously described the role of the P2X7 receptor in myeloma, a rare blood disease that uniquely presents with aggressive bone destruction. In this study, we used known agonists of the P2X7 receptor to induce calcium influx and YO-PRO-1 uptake in murine MOPC315.BM myeloma cells as readouts of P2X7 receptor-mediated channel activation and pore formation, respectively. Neither ATP- nor BzATP-induced calcium influx and YO-PRO-1 indicated an absence of the P2X7 receptor function on MOPC315.BM cells. TaqMan revealed low (Ct > 35) P2rx7 but high P2rx4 gene expression in MOPC315.BM; the latter was downregulated with BzATP treatment. The concomitant downregulation of CD39/Entpd1, Icam-1, and Nf-kb1 and the upregulation of Casp-1 genes regulated during purinergic signaling and with established roles in myeloma progression suggest P2RX4-mediated survival adaptation by cancer cells. Further studies are needed to characterize the P2RX4 pharmacology on MOPC315.BM since transcriptional regulation may be utilized by cancer cells to overcome the otherwise toxic effects of high extracellular ATP.
U2 - 10.3390/receptors2030013
DO - 10.3390/receptors2030013
M3 - Journal article
VL - 2
SP - 191
EP - 203
JO - Receptors
JF - Receptors
SN - 1048-6909
IS - 3
ER -
ID: 382382282