TY - JOUR
T1 - PRRX1 promotes malignant properties in human osteosarcoma
AU - Joko, Ryoji
AU - Yamada, Daisuke
AU - Nakamura, Masahiro
AU - Yoshida, Aki
AU - Takihira, Shota
AU - Takao, Tomoka
AU - Lu, Ming
AU - Sato, Kohei
AU - Ito, Tatsuo
AU - Kunisada, Toshiyuki
AU - Nakata, Eiji
AU - Ozaki, Toshifumi
AU - Takarada, Takeshi
N1 - Funding Information:
We thank Dr. Jones, K. B. for providing the paraffin-embedded tissue samples of mouse osteosarcoma. Preparation of slides and staining was supported by Central Research Laboratory, Okayama University Medical School. We thank the members of the Department of Animal Resources, Advanced Science Research Center, and Okayama University for maintaining the mice. This research was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to D.Y. (no. 18K15212 ) and E.N. (no. 19K09551 ), AMED under Grant Number JP19lm0203008 . These funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
We thank Dr. Jones, K. B. for providing the paraffin-embedded tissue samples of mouse osteosarcoma. Preparation of slides and staining was supported by Central Research Laboratory, Okayama University Medical School. We thank the members of the Department of Animal Resources, Advanced Science Research Center, and Okayama University for maintaining the mice. This research was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to D.Y. (no. 18K15212) and E.N. (no. 19K09551), AMED under Grant Number JP19lm0203008. These funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2020 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - 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 expressionon 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.
AB - 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 expressionon 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.
KW - Connectivity map analysis
KW - Drug resistance
KW - Invasion
KW - Osteosarcoma
KW - PRRX1
KW - Tumor malignancy
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U2 - 10.1016/j.tranon.2020.100960
DO - 10.1016/j.tranon.2020.100960
M3 - Article
AN - SCOPUS:85097780067
SN - 1944-7124
VL - 14
JO - Translational Oncology
JF - Translational Oncology
IS - 1
M1 - 100960
ER -
