골육종의 발암 기전에서 CD74의 역할 및 Macrophage Migration Inhibitory Factor와의 관계 (Role of CD74 and Its Relationship with Macrophage Migration Inhibitory Factor in Osteosarcoma Tumorigenesis)

서지정보

· 발행기관 : 대한정형외과학회
· 수록지 정보 : 대한정형외과학회지 / 52권 / 2호 / 192 ~ 198페이지
· 저자명 : 한일규, 안선희, 박종웅, 이용준, 김한수

초록

목적: CD74 (cluster of differentiation 74)는 골육종의 tumorigenesis와 연관된다고 알려진 macrophage migration inhibitory factor (MIF)와 결합한다. 본 연구의 목적은 CD74와 MIF의 연관성과 골육종의 발암에서 CD74의 역할을 규명하는 것이다.
대상 및 방법: CD74와 MIF의 연관성은 환자(n=45)에서 분리한 골육종 조직에 면역염색법을 이용하여 조사하였다. 환자 유래 골육종세포주(n=22)의 CD74 발현은 real-time polymerase chain reaction 방법으로 조사하였다. CD74와 골육종에서 cisplatin 항암작용의 내성과의 관계는 WST-1, colony forming 분석법을 이용하였다.
결과: 면역염색 결과 55.6%에서 MIF와 CD74가 모두 높게 나타났고. 88.9%에서 MIF가 높게 발현되었다. CD74 mRNA 발현은 모든 골육종세포에서 정상세포에 비해 높았다. Cisplatin 처리 후 CD74 mRNA 발현이 높은 세포에서 세포 성장억제력과 colony formation 방해능력은 감소하였다.
결론: CD74의 발현은 MIF의 발현과 상관관계를 보였다. 그리고 CD74는 골육종의 cisplatin 내성작용에서 역할을 할 것으로 판단된다.

영어초록

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.

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