Research for cell-basement membrane adhesion factors involved in distant metastasis of tumors using human tumor tissue.

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15381
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Kawai Hitomi 筑波大学, 医学医療系, 助教 (50895026)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 浸潤性粘液腺癌 / 細胞膜タンパク / モノクローナル抗体

Outline of Final Research Achievements

Introduction: Invasive mucinous adenocarcinoma (IMA) frequently shows aerogenous spread of lung adenocarcinoma, which can be considered as an early stage of distant metastasis.
Object: I produced monoclonal antibodies whose antigens were membranous proteins extracted from frozen tissue samples of IMA, then identified the antigen and functionally analyzed the antigenic protein, which was considered to be associated with aerogenous spread.
Result: Mass spectrometry of immunoprecipitated samples using monoclonal antibodies identified MRP2 as a candidate antigen, which is expressed on the cell membrane (especially at the apex) of lung adenocarcinoma cell lines (A549) and IMA, but not on non-neoplastic alveolar and bronchial epithelia, suggesting that MRP2 functions as a cancer-specific protein in the lung.

Free Research Field

肺腺癌

Academic Significance and Societal Importance of the Research Achievements

IMAは高頻度に経気道散布という遠隔転移形式を呈する。経気道散布は遠隔転移の初期段階状態と見なすことができる。今回、IMAの細胞膜タンパクを抗原としたモノクローナル抗体を作成し、抗原候補としてMRP2が同定された。本報告ではMRP2がIMAおよび肺腺癌細胞株の細胞膜に発現することを初めて報告した。MRP2は薬物や生理活性物質の流出入に関わるタンパクであり、IMAにおけるMRP2の異所性の発現が、癌細胞－炎症細胞間に癌特異的な生化学的カスケードが構築している可能性が考えられた。MRP2の発現が癌細胞ー基底膜間の接着に与える影響を調べることで、遠隔転移の初期段階の機序を解明する手がかりとなる。