PRRX1 promotes malignant properties in human osteosarcoma
| Autor: | Tomoka Takao, Aki Yoshida, Daisuke Yamada, Takeshi Takarada, Eiji Nakata, Ming Lu, Tatsuo Ito, Shota Takihira, Ryoji Joko, Toshifumi Ozaki, Masahiro Nakamura, Kohei Sato, Toshiyuki Kunisada |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Cancer Research Original article Biology lcsh:RC254-282 03 medical and health sciences Limb bud 0302 clinical medicine Downregulation and upregulation Invasion medicine neoplasms PRRX1 paired related homeobox 1 Connectivity map analysis Tumor malignancy Cisplatin Gene knockdown Osteosarcoma Mesenchymal stem cell Cell migration medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens 030104 developmental biology Oncology 030220 oncology & carcinogenesis Drug resistance Cancer research OS Osteosarcoma PRRX1 Immunostaining medicine.drug |
| Zdroj: | Translational Oncology Translational Oncology, Vol 14, Iss 1, Pp 100960-(2021) |
| ISSN: | 1936-5233 |
| Popis: | Highlights • PRRX1 is a poor-prognosis marker of human osteosarcoma. • PRRX1 promotes proliferation, invasion, and drug resistance in human osteosarcoma. • Forskolin was identified using RNA expression signatures of PRRX1 knockdown. • Forskolin decreased proliferation and migration in human osteosarcoma. 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. |
| Databáze: | OpenAIRE |
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