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ID 105907
Title Alternative
Pregnancy-associated plasma protein Aを悪性胸膜中皮腫細胞の遊走能を促進する遺伝子として同定 : 治療標的としての可能性
Author
Huang, Jun Department of Respiratory Medicine and Rheumatology, Institute of Health Biosciences, The University of Tokushima
Tabata, Sho The University of Tokushima
Kakiuchi, Soji The University of Tokushima
Van, Trung The The University of Tokushima
Goto, Hisatsugu The University of Tokushima KAKEN Search Researchers
Hanibuchi, Masaki The University of Tokushima KAKEN Search Researchers
Keywords
malignant pleural mesothelioma
pregnancy-associated plasma protein A
migration
orthotopic xenograft mouse model
Content Type
Thesis or Dissertation
Description
Despite recent advances in treatment, malignant pleural mesothelioma (MPM) remains a deadly disease. Targeted therapy generated broad interests and is highly expected for the treatment of MPM, yet promising preclinical results have not been translated into substantial clinical benefits for the patients. In this study, we tried to identify the genes which play functional roles in cell migration as well as to test whether they can be used as novel targets for molecular targeted therapy for MPM in preclinical model. In our study, pregnancy-associated plasma protein A (PAPPA) was identified as a gene whose expression level is correlated with MPM cell migration by correlation analysis combining MPM cell migration ability and their gene expression profiles. Highly migratory cells were selected from MPM cell lines, MSTO-211H, NCI-H290 and EHMES-1 in vitro and up-regulation of PAPPA in these cells were confirmed. In vitro, PAPPA was demonstrated to stimulate the MPM cell migration via cleavage of insulin-like growth factor-binding protein-4 and subsequent release of IGF-1. Gene silencing of PAPPA in MPM cells led to reduced migration, invasion and proliferation. Furthermore, PAPPA shRNA transfected NCI-H290 when orthotopically inoculated into pleural cavity of severe combined immunodeficiency recipient mice, failed to develop tumors and produce bloody pleural effusion as control shRNA transfected cells did. Our study suggests that PAPPA plays a functional role in promoting MPM cell migration and it might serve as a potential therapeutic target for the treatment of MPM.
Journal Title
Oncotarget
ISSN
19492553
Publisher
Impact Journals
Volume
4
Issue
8
Start Page
1172
End Page
1184
Published Date
2013-07-08
Remark
内容要旨・審査要旨・論文本文の公開:
内容要旨・審査要旨 : LID201310221002.pdf
論文本文 : LID201405231001.pdf
本論文は, 著者Jun Huangの学位論文として提出され, 学位審査・授与の対象となっている。
Rights
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,distribution, and reproduction in any medium, provided the original author and source are credited.( https://creativecommons.org/licenses/by/3.0/ )
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第2630号
Diploma Number
甲医第1173号
Granted Date
2013-09-12
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences