폐암세포 표면 단백질을 이용한 진단 및 치료방법의 개발

Abstract

Lung cancer is the most common cause of death throughout the world. In this respect, discovery of biomarkers, which can be developed as diagnosing and therapeutic target is quite important. Especially, cancer specific surface protein has an advantage that can be developed as an in vivo imaging target or therapeutic target biomarker. We had identified 134 membrane proteins that are not detected in normal tissue, but expressed in all 4 type of lung cancer cell lines. Among them, we choose 4 promising proteins to further validation. First, we prepared antibodies against extracellular region to directly monitor changes in the surface expression of candidate proteins. To determine lung cancer specific expression, we performed western blot analysis, flow cytometry, and immunocytochemistry. In addition, we had analyzed whether antibody treatment directly regulates lung cancer cell proliferation in vitro. By using western blot analysis, RT-PCR , and immunocytochemistry, we confirmed all the candidate proteins were exclusively expressed in cancer cell lines. Flow cytometry data shows us the specific binding of antibodies to cancer cell surface. And the more, antibodies attach to cancer cell surface and block the growth or kill the cancer cells in vitro. In addition, we found the shrinkage of lung cancer tissue in xenogragft model after antibody injection. In conclusion, the potential diagnostic and therapeutic agent was validated via monoclonal antibody against protein comparing difference of gene expression level between normal and lung cancer cell.