Role of CD74 and Its Relationship with Macrophage Migration Inhibitory Factor in Osteosarcoma Tumorigenesis / 대한정형외과학회잡지

ABSTRACT

PURPOSE: CD74 (cluster of differentiation 74) is a type II transmembrane protein that associates with MHC-II (major histocompatibility complex-II) molecules and binds with the macrophage migration inhibitory factor (MIF), which is known to be associated with tumorigenesis. The purpose of this study was to examine the relationship between CD74 with MIF and the role of CD74 in osteosarcoma tumorigenesis. MATERIALS AND METHODS: A correlation between CD74 with MIF was examined using immunohistochemistry (IHC) of tissues from patients with osteosarcoma (n=45). The mRNA expression of CD74 from patient-derived primary cells of osteosarcoma (n=22) was examined by a real-time polymerase chain reaction. The role of CD74 and in cisplatin-resistance of osteosarcoma was examined using WST-1 and colony forming assay. RESULTS: Of the 45 patients, 25 patients (55.6%) had a high level of expression in both CD74 and MIF by IHC. High level of MIF expression was observed in 40 patients (88.9%). We detected that mRNA expression of CD74 was higher in cells of all osteosarcoma patients (n=22) examined than in the control cells (hFOb 1.19). After cisplatin treatment, the inhibition of cell proliferation and suppression of colony formation were reduced in osteosarcoma cells expressing CD74. Interestingly, the effect of inhibiting anchorage independent growth was activated after cisplatin treatment in the cells with very high expression CD74 mRNA. CONCLUSION: This study suggests that the level of CD74 expression correlates with that of MIF expression. Moreover, CD74 might have a role in cisplatin resistance of osteosarcoma.