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
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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
Hanibuchi, Masaki
The University of Tokushima
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Nishioka, Yasuhiko
The University of Tokushima
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Keywords | malignant pleural mesothelioma
pregnancy-associated plasma protein A
migration
orthotopic xenograft mouse model
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Content Type |
Thesis or Dissertation
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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.
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Journal Title |
Oncotarget
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ISSN | 19492553
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Publisher | Impact Journals
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Volume | 4
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Issue | 8
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Start Page | 1172
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End Page | 1184
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Published Date | 2013-07-08
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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/ )
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
ETD
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MEXT report number | 甲第2630号
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Diploma Number | 甲医第1173号
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Granted Date | 2013-09-12
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Degree Name |
Doctor of Medical Science
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Grantor |
Tokushima University
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departments |
Medical Sciences
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