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Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Expression and function of PIM kinases in osteosarcoma
Shuai Mou1, Guangbin Wang1, Ding Ding2
1Department of Orthopaedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Abstract:
The provirus integrating site Moloney murine leukemia virus (PIM) family of serine/threonine protein kinases is composed of three members, PIM1, PIM2 and PIM3, which have been identified as oncoproteins in various malignancies. However, their role in osteosarcoma (OS) remains largely unknown. This study aimed to examine the expression patterns and the clinical significance of PIM kinases in human OS and their biological effects in human OS cell lines. Immunohistochemical staining was used to detect PIM kinases in archived pathologic material from 43 patients with primary OS; in addition, the effects of PIM knockdown and overexpression on the proliferation, migration and invasion of OS cell lines were determined. We observed that all three PIM kinases were frequently expressed in OS, but only PIM1 positive expression was associated with poorer prognosis regarding overall survival of OS patients. In addition, knockdown of PIM kinases notably inhibited OS cell proliferation, migration and invasiveness, whereas overexpression of PIM kinases resulted in increased OS cell growth and motility. This study suggests that PIM1 could be a valuable prognostic marker in patients with OS, and the biological functions of PIM kinase family in the osteosarcoma cell lines indicate that they could serve as potential therapeutic targets for OS.
Insights
PIM kinases are frequently expressed in osteosarcoma (OS). PIM1 expression indicates poorer prognosis, and PIM kinase inhibition may offer new therapeutic strategies for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The PIM (provirus integrating site Moloney murine leukemia virus) kinase family, comprising PIM1, PIM2, and PIM3, are serine/threonine protein kinases implicated as oncoproteins in various cancers.
- The specific role and clinical significance of PIM kinases in osteosarcoma (OS) pathogenesis are not well-established.
Purpose of the Study:
- To investigate the expression patterns of PIM1, PIM2, and PIM3 in human osteosarcoma.
- To evaluate the clinical significance of PIM kinase expression in relation to patient prognosis.
- To determine the biological effects of PIM kinase modulation on osteosarcoma cell behavior.
Main Methods:
- Immunohistochemical staining was employed to assess PIM kinase expression in 43 primary osteosarcoma tissue samples.
- Functional studies involved PIM kinase knockdown and overexpression in human osteosarcoma cell lines to analyze effects on proliferation, migration, and invasion.
Main Results:
- All three PIM kinases (PIM1, PIM2, PIM3) were frequently detected in osteosarcoma tissues.
- Positive PIM1 expression correlated significantly with poorer overall survival in osteosarcoma patients.
- PIM kinase inhibition markedly reduced osteosarcoma cell proliferation, migration, and invasiveness.
- Conversely, PIM kinase overexpression led to enhanced osteosarcoma cell growth and motility.
Conclusions:
- PIM1 may serve as a valuable prognostic biomarker for osteosarcoma patients.
- The PIM kinase family plays a significant role in osteosarcoma cell biology, suggesting their potential as therapeutic targets for this malignancy.
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