Identification of Abnormal Spindle Microtubule Assembly as a Promising Therapeutic Target for Osteosarcoma

Orthop Surg. 2020 Dec;12(6):1963-1970. doi: 10.1111/os.12796. Epub 2020 Oct 20.

Abstract

Objective: To demonstrate the expression of abnormal spindle microtubule assembly (ASPM) in clinical osteosarcoma tissue specimens collected in our hospital, and to explore the function of ASPM in osteosarcoma in vitro and in vivo.

Methods: Tissue specimens from 82 cases of osteosarcoma were collected and analyzed by immunohistochemistry assay. We also investigated the relationship between ASPM expression and clinicopathological characteristics in the patients. We transfected shASPM plasmid and the empty control plasmid, respectively, and then used quantitative polymerase chain reaction and western blot analysis to detect ASPM expression. Cell colony assay and MTT were used to observe the proliferation ability. In vivo study was undertaken to explore the ASPM function further.

Results: In this study, ASPM showed high expression in osteosarcoma tissue samples compared with non-tumor normal tissues. ASPM was positively correlated with clinical pathological characteristics, including tumor size (P = 0.024) and clinical stage (P = 0.045). Our results further showed that ASPM depletion dramatically inhibited the proliferation of osteosarcoma cells (with fewer cells in the sh-RNA-ASPM group compared with the control group(P < 0.05, respectively), and the in vivo assays further confirmed that ASPM ablation markedly blocked tumor growth compared with control (P < 0.05).

Conclusion: Our data provides strong evidence that the high expression of ASPM in osteosarcoma promotes proliferation in vitro and in vivo, indicating its potential role as an osteosarcoma therapeutic target.

Keywords: ASPM; In vitro and in vivo; Osteosarcoma; Proliferation; Therapeutic target.

MeSH terms

  • Animals
  • Bone Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Targeted Therapy / methods*
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / pharmacology*
  • Osteogenesis / drug effects*
  • Osteosarcoma / metabolism*
  • RNA, Small Interfering / physiology
  • Transfection
  • Tumor Burden

Substances

  • ASPM protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • RNA, Small Interfering