Nicotinamide Phosphoribosyl Transferase Is Increased in Osteosarcomas and Chondrosarcomas Compared to Benign Bone and Cartilage

Abstract

Background/Aim: Primary bone neoplasms include osteosarcomas (OS), chondrosarcomas (CS), and giant cell tumors (GCT). Nicotinamide phosphoribosyl transferase (NAMPT) catalyzes the rate-limiting step of nicotinamide adenine dinucleotide synthesis and is increased in multiple tumor types. In malignancies, NAMPT expression often correlates positively with tumor grade, chemotherapy resistance, and metastatic potential. Materials and Methods: Tissue microarray was used to examine NAMPT expression in benign bone and cartilage, GCTs, OS, and different CS grades. Results: For the first time, we showed that NAMPT expression was increased in GCTs and OS compared to benign bone, and in CS compared to benign cartilage. Its expression also increased with higher CS grade. Conclusion: Our data indicate that NAMPT plays a role in bone sarcomas and GCTs, and its higher expression may contribute to increased tumor aggressiveness. Malignancies of the bones and joints are rare, comprising 0.2% of all human neoplasms. In the United States, approximately 3,450 were diagnosed in 2017, while in the same year these malignancies caused 1,590 deaths (1, 2). Among these malignancies, osteosarcomas (OS) and chondrosarcomas (CS) constitute 36% and 20-25% of bone and joint malignancies, respectively (1-3). While OS can occur in patients of all ages, it exhibits a bimodal distribution, with disease peaks at 15-19 years and 75-79 years (1-3). Although most cases are sporadic, factors such as radiation exposure, Paget's disease of the bone, and genetic susceptibilities increase OS risk (1-4). They commonly present in the long bones at areas of rapid bone growth, typically adjacent to the metaphyseal growth plate, commonly at the proximal humerus and tibia, and distal femur (1-4). OS is more common in males and confers different survival rates by different ages and anatomic locations (1-4). In adolescents and children, the 5-year survival rate is approximately 55-75%, with older individuals having an approximately 57% 5year survival rate that falls with increasing age (1-4). Histologically, OS exhibit malignant pleomorphic cells with an osteogenic differentiation that produces osteoid, typically in irregular trabeculae (1-4). While malignant bone is always present, the matrix of conventional OS may have chondroid, fibroblastic, or cartilaginous features (1-4). Less common OS subtypes include telangiectatic, small-cell, periosteal, paraosteal, extraskeletal, and secondary OS (1-4). CS are adult bone sarcomas and often present as slowgrowing heterogenous malignancies in individuals between 30 and 60 years old (2-3, 5). CS are associated with a 5-year survival rate of approximately 70%, are slightly more common in males, and commonly occur in the lower limbs, pelvis, sternum, ribs, and clavicle (2-3, 5). CS is often graded on a I-III scale, with 90% graded I-II and 5-10% grade III, which carry significant metastatic potential (2-3, 5). CS is classified as primary if not associated with a preexisting chondroid lesion and secondary if they it is, often...

Long Noncoding RNA NORAD/MiR-26a-5p/NAMPT (Visfatin) Axis Regulates Proliferation and Apoptosis of Human Osteosarcoma Cells

“…By using TargetScan V7.2 and dual-luciferase reporter assay in our work, we predicted and con rmed that miR-26a-5p possess a binding site of NORAD and NAMPT, respectively. NAMPT is elevated in OS compared to benign bone (22). NORAD is observed to be conspicuously overexpressed in both OS cells and OS tumors (16).…”

Silencing of NAMPT leads to up-regulation of insulin receptor substrate 1 gene expression in U87 glioma cells

“…The values of these mRNA expressions were normalized to the expression of beta-actin mRNA, expressed as mean ± SEM and represented as a percent of control (100%); n=4. and progression (Minchenko et al 2015a;Feng et al 2016;Alaee et al 2017;Lucena-Cacace et al 2017;Xu et al 2017;Zhao et al 2017;Hesari et al 2018;Meram et al 2019).…”

“…The nicotinamide phosphoribosyltransferase (NAMPT) also known as visfatin and PBEF (pre-Bcell colony-enhancing factor) is an insulin-mimetic adipokine with anti-diabetic properties, which is involved in many important biological processes, including metabolism, stress response, insulin resistance, and tumorigenesis (Flehmig et al 2014;Olszanecka-Glinianowicz et al 2014;Minchenko et al 2015a;Carbone et al 2017;Hesari et al 2018;Annie et al 2019;Meram et al 2019). This protein catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate yielding to nicotinamide mononucleotide, the rate limiting component in the mammalian NAD biosynthesis pathway.…”

Targeting the NAD Salvage Synthesis Pathway as a Novel Therapeutic Strategy for Osteosarcomas with Low NAPRT Expression

“…Cancer cells rely mostly on the classical NAD+ synthesis pathway as de novo synthesis from amino acids is inefficient and the alternative pathway is often inactive due to the lack of expression of NAPRT1 [13,14]. In osteosarcoma, NAMPT is overexpressed as compared to that found in normal bone [15]. Targeting NAMPT could therefore potentially be a novel therapeutic option for osteosarcoma patients; consequently, the main aim of this study is to test the sensitivity of osteosarcoma cells to NAMPT inhibition.…”