The development of combined cancer therapy targeting hypoxic microenvironment

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590448
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hokkaido University (2013-2014); Sapporo Medical University (2012)
• Principal Investigator: TAMURA Yasuaki 北海道大学, フード&メディカルイノーべーション推進本部, 特任教授 (80322329)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 低酸素 / 酸化酵素 / 分子標的治療 / がんワクチン / MHC クラスI分子 / ジスルフィド結合 / ERO1-α / PDI

Outline of Final Research Achievements

ERO1-α is an ER-resident oxidase. ERO1-α and PDI play a central role in disulfide bond formation of secreted and cell surface molecules. We have recently demonstrated that various types of tumor cells expressed high levels of ERO1-α. In this study, we show that ERO1-α associates with PDI, calnexin and immature MHC class I before being incorporated into transporter-associated with antigen processing-1 (TAP-1)-associated peptide-loading complex. Importantly, ERO1-α regulates the redox state as well as cell surface expression of MHC class I, leading to alteration of susceptibility by CD8+ T cell. Similarly, the ERO1-α expression within cancer cells was associated with the expression level of MHC class I in colon cancer tissues. Thus, the cancer-associated ERO1-α regulates the expression of MHC class I molecule via oxidative protein folding within hypoxic tumor microenvironment.

Free Research Field

病理学