ID | 61318 |
FullText URL | |
Author |
Joko, Ryoji
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Yamada, Daisuke
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Nakamura, Masahiro
Precision Health, Department of Bioengineering, Graduate School of Engineering, The University of Tokyo
Yoshida, Aki
Department Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takihira, Shota
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takao, Tomoka
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Lu, Ming
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Sato, Kohei
Department Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kunisada, Toshiyuki
Department Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
researchmap
Nakata, Eiji
Department Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Ozaki, Toshifumi
Department Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
publons
researchmap
Takarada, Takeshi
Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
|
Abstract | Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.
|
Keywords | PRRX1
Osteosarcoma
Tumor malignancy
Invasion
Drug resistance
Connectivity map analysis
|
Published Date | 2021-01
|
Publication Title |
Translational Oncology
|
Volume | volume14
|
Issue | issue1
|
Publisher | Elsevier
|
Start Page | 100960
|
ISSN | 1936-5233
|
Content Type |
Journal Article
|
language |
English
|
OAI-PMH Set |
岡山大学
|
Copyright Holders | © 2020 The Authors.
|
File Version | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.1016/j.tranon.2020.100960
|
License | http://creativecommons.org/licenses/by-nc-nd/4.0/
|
Funder Name |
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
|
助成番号 | 18K15212
19K09551
JP19lm0203008
|