Claudin-18 and tumor microenvironment

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K15084
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Takasawa Kumi 札幌医科大学, 医学部, 助教 (50359709)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: クローディン18 / タイト結合 / がん微小環境

Outline of Final Research Achievements

In normal tissues, a tight junction protein claudin-18.2 (CLDN18) shows stomach-specific expression pattern. Recent studies have revealed that CLDN18 is aberrantly expressed in tumors derived from various organs and is associated with poor prognosis. In our previous studies, we have reported that CLDN18 is aberrantly expressed in pancreatic and bile duct cancers by using immunohistochemistry on surgical specimens and that CLDN18 contributes to malignant potentials of bile duct cancer cells.
In the present study, we confirmed that expression of CLDN18 was altered under several culture conditions mimic to tumor microenvironment by using Western blotting and immunofluorescence and evaluated tight junctional functions under the conditions. We performed comparative shotgun proteome analysis to identify candidate molecules which is associated with aberrant expression of CLDN18 and evaluated the expression pattern and interaction with CLDN18.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

クローディン18に関する研究では、claudiximab(抗クローディン18抗体)の胃がんに対する臨床治験が行われており、未治療群と比べて有意に予後を改善するという良好な結果が報告されている。今後、クローディン18が高発現する他臓器がんへの適応の拡大も期待され、いまだ判然としない claudiximab の抗腫瘍効果発現機序の解明は重要課題となっている。がんにおけるクローディン18発現とがん微小環境の相互作用を理解することは、学術的意義にとどまらず、がんの新規治療戦略構築にも貢献し得る。