난소암에서 인체 백혈구항원-G의 발현 분석
Analysis of Human Leukocyte Antigen-G Expression in Ovarian Cancer
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목적 : 인체 백혈구항원-G는 비전형 주조직적합체에 하나로서 극히 제한된 인체 조직에서만 관찰되며, 자연살해세포가 종양세포를 용해하지 않도록 보호할 수 있는 것으로 알려져 왔다. 난소암 세포주와 조직에서 인체 백혈구항원-G의 발현양상에 대한 분석을 통하여 난소암에서 인체 백혈구항원-G의 잠재적 역할을 알아보고자 본 연구를 시행하였다. 연구 방법 : 난소암 세포주인 OVCAR-3, SKOV-3, ES-2, PA-1, TOV-112D, TOV-21G와 13예의 난소암 조직에서 mRNA 수준의 인체 백혈구항원-G의 발현을 역전사 중합효소 연쇄반응을 통하여 조사하였고, 단백질 수준의 발현은 변성된 인체 백혈구항원-G 중쇄에 대한 단클론 항체인 MEM-G1을 이용하여 Western blot 분석과 면역조직화학염색을 통하여 확인하였다. 결과 : PA-1을 제외한 OVCAR-3, SKOV-3, ES-2, TOV-112D, TOV-21G 난소암 세포주에서 인체 백혈구항원-G isoform의 mRNA 전사물이 발현되었고, 단백질 수준에서의 발현도 Western blot 분석에 의하여 관찰되었다. 면역조직화학염색에 의하여 조사한 인체 백혈구항원-G의 단백질 발현은 난소암 조직 13예 중 8예에서 관찰되었다. 결론 : 본 연구 결과는 종양세포가 시험관내, 신체내 환경에서 세포독성 항종양 반응에 대한 회피를 위하여 어떻게 선택되어지는 가에 대한 단서를 제공하는 것으로서, 인체 난소암에서 인체 백혈구항원-G의 발현이 면역회피를 위한 하나의 기전으로 작용 할 수 있을 것으로 사료된다.
Abstract
Objective : Human leukocyte antigen-G (HLA-G) is a nonclassical major histocompatibility complex (MHC) molecule with highly limited tissue distribution that has been proposed to protect tumor cells from natural killer cell lysis. To delineate the potential role of HLA-G in ovarian cancer, we investigated expression patterns of this molecule in human ovarian cancer cell lines and tissues. Methods : HLA-G expression was determined both at RNA level by reverse transcriptase-polymerase chain reaction (RT-PCR) and protein level by Western blotting and immunohistochemistry using monoclonal antibody against denatured heavy chain of HLA-G, MEM-G1, in 13 ovarian cancer patient tissues and 6 ovarian cancer cell lines (OVCAR-3, SKOV-3, ES-2, PA-1, TOV-112D, TOV-21G). Results : We found mRNA transcripts of different HLA-G isoforms in five of 6 ovarian cancer cell lines (OVCAR-3, SKOV-3, ES-2, TOV-112D, TOV-21G). HLA-G protein was also detected in 5 cell lines that exhibited expression of HLA-G mRNA transcripts. Immunohistochemical analysis of human ovarian cancers revealed expression of HLA-G in eight of 13 tissue samples. Conclusion : Our results provide additional clues as to how a tumor can be selected in vitro and in vivo to escape from cytotoxic anti-tumor responses. We suggest that the aberrant expression of HLA-G may contribute to immune escape in human ovarian cancer.
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