SPRR1A is a potential therapeutic target for osteosarcoma: in vitro and in vivo evaluations using generated artificial osteosarcoma cancer stem cell‑like cells

Miyamoto,Tomohiro; Fukase,Naomasa; Kawamoto,Teruya; Fujiwara,Shuichi; Hara,Hitomi; Sawada,Ryoko; Nakamatsu,Yuta; Mifune,Yutaka; Kakutani,Kenichiro; Hoshino,Yuichi; Hayashi,Shinya; Matsumoto,Tomoyuki; Matsushita,Takehiko; Koyanagi‑Aoi,Michiyo; Aoi,Takashi; Takemori,Toshiyuki; Yahiro,Shunsuke; Kuroda,Ryosuke; Akisue,Toshihiro

doi:10.3892/or.2024.8857

SPRR1A is a potential therapeutic target for osteosarcoma: in vitro and in vivo evaluations using generated artificial osteosarcoma cancer stem cell‑like cells

Authors:
- Tomohiro Miyamoto
- Naomasa Fukase
- Teruya Kawamoto
- Shuichi Fujiwara
- Hitomi Hara
- Ryoko Sawada
- Yuta Nakamatsu
- Yutaka Mifune
- Kenichiro Kakutani
- Yuichi Hoshino
- Shinya Hayashi
- Tomoyuki Matsumoto
- Takehiko Matsushita
- Michiyo Koyanagi‑Aoi
- Takashi Aoi
- Toshiyuki Takemori
- Shunsuke Yahiro
- Ryosuke Kuroda
- Toshihiro Akisue
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Affiliations: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan, Department of Orthopaedic Surgery, Konan Medical Center, 658‑0064 Kobe, Japan, Division of Stem Cell Medicine, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan, Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673‑8558, Japan
Published online on: December 16, 2024 https://doi.org/10.3892/or.2024.8857
Article Number: 24
Copyright: © Miyamoto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cancer stem cells (CSCs) have been implicated as critical mediators in the progression, chemoresistance and metastatic capabilities of diverse malignancies, including osteosarcoma (OS). The authors have succeeded in generating CSC‑like cells (MG‑OKS) from the OS cell line MG‑63 by transducing defined factors. A significant increase in small proline‑rich protein 1A (SPRR1A) expression, a cross‑linked envelope protein in keratinocytes, was observed in MG‑OKS cells. Therefore, SPRR1A could be involved in tumor initiation, growth and poor OS progression. However, its specific role in OS remains unclear. The present study aimed to evaluate the role of SPRR1A in OS both in vitro and in vivo using MG‑OKS cells. Three experimental groups were established: MG‑OKS cells transfected with SPRR1A small interfering (si)RNA (siMG‑OKS), untransfected MG‑OKS cells and MG‑OKS cells transfected with scrambled siRNA (scMG‑OKS) as controls. SPRR1A expression, morphological changes, cell proliferation and migration were assessed in these groups. RNA sequencing was performed to examine the genetic changes caused by SPRR1A suppression. To evaluate tumorigenicity in vivo, cells from each group were subcutaneously transplanted into the backs of nude mice. Tumor volume and Ki‑67 expression were assessed and compared among the three groups at four weeks post‑transplantation. The siMG‑OKS group exhibited altered cell morphology, reduced cell proliferation and decreased migratory abilities in vitro. RNA sequencing revealed suppression of genes involved in cell adhesion in the siMG‑OKS group. Furthermore, the in vivo tumorigenicity of siMG‑OKS was lower than that of the other two experimental groups. These findings suggest that SPRR1A is one of the key cell adhesion‑related molecules involved in OS progression, potentially serving as a therapeutic target for this refractory tumor. However, further research is needed to fully elucidate the mechanisms by which SPRR1A influences OS pathogenesis and to explore its clinical potential.

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