Effect of P2X purinergic receptors in tumor progression and as a potential target for anti-tumor therapy

Abstract

The development of tumors is a complex pathological process involving multiple factors, multiple steps, and multiple genes. Their prevention and treatment have always been a difficult problem at present. A large number of studies have proved that the tumor microenvironment plays an important role in the progression of tumors. The tumor microenvironment is the place where tumor cells depend for survival, and it plays an important role in regulating the growth, proliferation, apoptosis, migration, and invasion of tumor cells. P2X purinergic receptors, which depend on the ATP ion channel, can be activated by ATP in the tumor microenvironment, and by mediating tumor cells and related cells (such as immune cells) in the tumor microenvironment. They play an important regulatory role on the effects of the skeleton, membrane fluidity, and intracellular molecular metabolism of tumor cells. Therefore, here, we outlined the biological characteristics of P2X purinergic receptors, described the effect of tumor microenvironment on tumor progression, and discussed the effect of ATP on tumor. Moreover, we explored the role of P2X purinergic receptors in the development of tumors and anti-tumor therapy. These data indicate that P2X purinergic receptors may be used as another potential pharmacological target for tumor prevention and treatment.

Keywords: ATP; P2X purinergic receptors; Tumor microenvironment; Tumors.

Fig. 1

The internal correlation between ATP in tumor microenvironment and tumor. Tumor microenvironment contains a variety of components, such as tumor-associated macrophages, bone marrow-derived suppressor cells, T lymphocytes, fibroblasts, extracellular matrix, ATP, tumor cells, and growth factors. These components constitute the environment in which tumor cells depend on survival. ATP is secreted into the microenvironment through tumor cells and other cells, acts on immune cells (such as CD39, CD26, CD72 cells) and other molecular substances (such as P2X purinergic receptors), hydrolyzes into ADP, AMP, and adenosine, further acts on other immune cells (such as macrophages, NK cells, and dendritic cells), and exerts immune functions, thereby regulating the progression of tumor cells

Fig. 2

Potential correlation between P2X7 receptor and tumor development. After tumorigenesis, cells (such as tumor cells and immune cells) release a large amount of ATP into the extracellular matrix, resulting in a sharp increase in ATP concentration, activating P2X7 receptor and opening ion channels on the cell membrane (sodium ions, calcium ions influx, and potassium ions outflow), activating intracellular signaling pathways (such as NF-kB, MAPK, mTOR, and JNK), and regulating gene transcription in the nucleus, thereby affecting the progression of tumor cells (promoting growth or inhibiting proliferation)