The non functional-P2X7-receptor in pediatric solid tumors

Introduction:

The P2X₇-receptor is a homotrimeric, ATP-gated ion channel responsible for controlling a diverse range of cell functions, including apoptosis, cell migration and cell proliferation. On the surface of diverse cancer cells, the receptor has been found to be partially non-functional. Due to conformational changes, the nfP2X7 receptor is unable to form a large pore conformation of the channel when exposed to high concentrations of ATP and can't induce apoptosis anymore. However, the receptor is still able to function as a calcium channel that promotes cell invasion. The nfP2X7 receptor exposes epitopes on the cell membrane that are hidden in fully functional P2X7. Furthermore, it has been shown that a change of conformation by binding of a specific antibody to the nf-P2X₇-receptor leads to cell death in vitro. These characteristics of the nfP2X7 receptor provide a perfect target for detection and treatment of cancer. Our aim was to assess the nfP2X7 receptor and its potential role as a therapeutic target on pediatric solid tumor cell lines.

Methods:

We used flow cytometry and western blot for expression analysis of the nfP2X7 receptor in pediatric tumor cell lines as well as immunohistochemistry staining for patient samples. Furthermore we examined the anti-tumor activity of the antibody against nf-P2X₇-receptor using viability, ADCC and migration assays.

Results:

We observed varying expression levels of the nf-P2X₇-receptor on all investigated cell lines: rhabdomyosarcoma, ewing sarcoma, osteosarcoma, neuroblastoma, hepatoblastoma, hepatocellular carcinoma, and wilms tumor. Unfortunately, we did not see an anti-tumor activity after incubation with the specific antibody against the nf-P2X₇-receptor.

Conclusions:

In summary, the nf-P2X₇ receptor potentially represents a promising target for tumor cells which provides an opportunity for developing biomarkers and precise methods of detecting tumor recurrence in pediatric tumor patients.