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Up-regulation of matrix metalloproteinase-9 in primary bone tumors and its association with tumor aggressiveness

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Abstract

Background

Understanding the molecular mechanism underlying the pathophysiology of primary skeletal tumors is crucial due to the tumor-related complications, incidence at a young age, and tumor recurrence.

Methods and results

The local expression pattern of MMP-9 as an active matrix-degrading protease was detected in 180 bone tissues, including 90 tumors and 90 noncancerous tissues, utilizing real-time qRT-PCR at the mRNA level and immunohistochemistry at the protein level. The correlation of the MMP-9 expression level with the patient's clinical pathological characteristics and the aggressiveness of the tumor was evaluated. The diagnostic significance of MMP-9 and the model of association of variables and MMP-9 expression and their predictive values were determined. Mean mRNA expression was higher in all types of primary bone tumors than their paired non-cancerous tissues. Osteosarcoma and Ewing's sarcoma expressed higher levels of MMP-9 compared to benign giant cell tumors, and the MMP-9 expression level was significantly correlated with the size, metastasis, and recurrence of the malignant tumor. A consistent expression pattern was demonstrated for MMP-9 protein levels in tissues. In addition, the MMP-9 gene and protein levels significantly discriminate between bone tumors and normal tissue, as well as benign and malignant tumors, and could predict potentially malignant traits such as tumor grade and metastasis.

Conclusions

The data propose that MMP-9 may be involved in the proliferation and invasion of primary bone tumors and has the potential to monitor and treat the progression of malignant tumors.

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Abbreviations

MMP:

Matrix metalloproteinase

GCT:

Giant cell tumor

OCT:

Optimal cutting temperature

ROC:

Receiver operating characteristic

AUC:

Area under the curve

Std:

Standard deviation

ALP:

Alkaline phosphatase

IDH2:

Isocitrate dehydrogenase 2

NF-κB:

Nuclear factor-κB

CSC:

Cancer stem cell

ECM:

Extra-cellular matrix

NSCLC:

Non-small cell lung cancer

EV:

Extracellular vesicles

PDAC:

Pancreatic ductal adenocarcinoma

ECD:

Extracellular domain level

TNF alpha:

Tumor necrosis factor alpha

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Acknowledgements

This work was financially supported by the Iran University of Medical Sciences (Grant Number: 1400-1-4-20559). We deeply appreciate all the patients who made this study possible by generously providing us with their tissue samples.

Funding

This work was financially supported by the Iran University of Medical Sciences (Grant Number: 1400-1-4-20559).

Author information

Authors and Affiliations

  1. Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614535, Tehran, Iran

    Mohammad Amin Vaezi, Amir Reza Eghtedari, Banafsheh Safizadeh, Ghasem Ghasempour, Mitra Nourbakhsh & Masoumeh Tavakoli-Yaraki

  2. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

    Vahid Salimi

  3. Department of Laboratory Medicine, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Shima Nazem

Authors
  1. Mohammad Amin Vaezi
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  2. Amir Reza Eghtedari
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  3. Banafsheh Safizadeh
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MAV, ARE, BS, GG, VS, MN, SN. The first draft of the manuscript was written by MT and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masoumeh Tavakoli-Yaraki.

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Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The project was ethically approved by the ethics committee of the Vice president of research of Iran University of Medical Sciences with ethics committee code: IR.IUMS.FMD.REC.1400.393. All participants were informed before surgery and following the informed consent, they were included in the study. The signed consent form for each patient is available.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent to publish

The authors affirm that human research participants provided informed consent for publication of the data in Table 2 and Fig. 4.

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Vaezi, M.A., Eghtedari, A.R., Safizadeh, B. et al. Up-regulation of matrix metalloproteinase-9 in primary bone tumors and its association with tumor aggressiveness. Mol Biol Rep 49, 9409–9427 (2022). https://doi.org/10.1007/s11033-022-07798-z

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  • DOI: https://doi.org/10.1007/s11033-022-07798-z

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