CD38 affects the biological behavior and energy metabolism of nasopharyngeal carcinoma cells

Abstract

Nasopharyngeal carcinoma (NPC) is the most common malignant tumor type in Southern China and South-East Asia. Cluster of differentiation (CD)38 is highly expressed in the human immune system and participates in the activation of T, natural killer and plasma cells mediated by CD2 and CD3 through synergistic action. CD38 is a type II transmembrane glycoprotein, which was observed to mediate diverse activities, including signal transduction, cell adhesion and cyclic ADP-ribose synthesis. However, the significance of CD38 in NPC biological behavior and cellular energy metabolism has not been examined. In order to elucidate the effect of CD38 on the biological behavior of NPC cells, stable CD38-overexpressed NPC cell lines were established. It was demonstrated that CD38 promoted NPC cell proliferation with Cell Counting Kit-8 and colony formation assays. It was also indicated that CD38 inhibited cell senescence, and promoted cell metastasis. Furthermore, it was determined that CD38 promoted the conversion of cells to the S phase and decreased the content of reactive oxygen species and Ca2+. Additionally, cell metabolism assays demonstrated that CD38 increased the concentration of ATP, lactic acid, cyclic adenosine monophosphate and human ADP/acrp30 concentration in NPC cells. To investigate the possible mechanism, bioinformatics analysis and mass spectrometry technology was used to determine the most notably changing molecule and signaling pathways, and it was determined and verified that CD38 regulated the metabolic-associated signaling pathways associated with tumor protein 53, hypoxia inducible factor-1α and sirtuin 1. The present results indicated that CD38 may serve a carcinogenic role in NPC by regulating metabolic-associated signaling pathways.

CD38 Multi-Functionality in Oral Squamous Cell Carcinoma: Prognostic Implications, Immune Balance, and Immune Checkpoint

“…CD38 research originally focused on hematological tumors, including CLL and multiple myeloma. However, with more research expanding the field, CD38 has been confirmed as expressed in multiple types of solid tumors such as nasopharyngeal cancer ( 19 ), cervical cancer ( 20 ), and skin cutaneous melanoma ( 21 ). CD38 is a non-lineage restricted glycoprotein expressed in both non-hematopoietic cells and diverse immune cells.…”

High CD38 expression in tumor-infiltrating immune cells is a favorite prognosis factor in esophageal squamous cell carcinoma with perigastric lymph node metastasis

“…CD38 converts NAD + to ADP − ribose (ADPR) and cADPR, which are essential for regulating extracellular metabolites, intracellular Ca2 + level, cell adhesion, and signal transduction pathways [20]. CD38 inhibited the nasopharyngeal carcinoma (NPC) cells apoptosis by regulating intracellular Ca2 + concentration, ATP concentration and reactive oxygen species (ROS) signals [10]. CD38 inhibited CD8 + T-cell proliferation through producing adenosine [21].…”

“…One previous study reported that CD38 reduced tumor cell senescence and increased cell metastasis in nasopharyngeal carcinoma [10]. Moreover, Zhang, et al found that the high expression of CD38 was correlated with the poor prognosis of pancreatic ductal adenocarcinoma [11].…”

IFN-γ and CD38 in Hyperprogressive Cancer Development

“…Moreover, tumor hypoxia recruits Treg cells in the TME via the upregulation of chemokines, while the increased expression of FasL on the tumor endothelial barrier in hypoxic conditions can selectively eliminate effector CD8 + T cells. Increased expression of ANGPT2 mRNA in mononuclear cells of untreated CLL patients has been associated with high CD38 expression [ 219 ], which influences the expression of hypoxia-inducible factor 1-alpha (HIF-1α) [ 220 ]. The overexpression of HIF-1α has been associated with poor prognosis and an aggressive phenotype in several malignant tumors [ 221 , 222 , 223 ].…”