Mechanism of tumor adaptation to the three-dimensional adhesion environment

2015 Fiscal Year Final Research Report

• Project/Area Number: 25870947
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; Tumor biology
• Research Institution: Tokyo University of Science
• Principal Investigator: Nagano Makoto 東京理科大学, 基礎工学部, 研究員 (50572715)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: がん増殖 / がん悪性化 / 細胞-ECM間接着

Outline of Final Research Achievements

In this study, I focus on the regulatory mechanism to adapt tumor cells to survive in the three-dimensional cell－extracellular matrix adhesion environment. First, I established the MKN7-derived cell, which has acquired growth actvity in the 3D environment. To identify the key proteins in 3D growth of the cells, I compared the levels of the expression or the phosphorylation of the multiple proteins including signal-, oncology- or stress-related molecules, to the parental MKN7 cells. I elucidated that the phosphorylation of STAT3 is promoted and the down-stream target Bcl-x, which has a suppressive role in the apoptosis, is increased. Furthermore, several proteases such as MMP-9, Cathepsin L are increased, whereas some types of protease inhibitors including HAI-I/2, Maspin are decreased. These results suggest that the apoptosis suppression via STAT-3 signaling and the some types of protease activity are crucial for the tumor adaptation to the three-dimensional adhesion environment.

Free Research Field

がんの細胞生物学