Upregulation of Matrix Metalloproteinases in the Metastatic Cascade of Breast Cancer to the Brain

Kamalabadi Farahani, Mohammad; Atashi, Amir; Bitaraf, Fateme Sadat

doi:10.31557/APJCP.2023.24.9.2997

Upregulation of Matrix Metalloproteinases in the Metastatic Cascade of Breast Cancer to the Brain

Document Type : Research Articles

Authors

¹ Department of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

² Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences, Shahroud, Iran.

³ Department of Medical Biotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.

10.31557/APJCP.2023.24.9.2997

Abstract

Background: In patients with triple-negative breast cancer (TNBC), brain metastasis is a fatal consequence. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 as the major members of the MMP family, are involved in many different facets of breast cancer metastasis. Aims: In this study, we sought the MMPs expression in the metastatic cascade of TNBC. Methods and results: Primary breast cancer cells known as 4T1T were extracted from the tumor mass following the creation of an animal model of TNBC. The brain metastasis lesions of malignant mice were used to extract highly brain metastatic tumor cells known as 4T1B. Gelatinase zymography and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of MMPs at the proteomic and transcriptomic levels in 4T1T and 4T1B. Our results indicated; brain metastatic tumor cells greatly increased their expression of MMPs. In 4T1B, MMP-2 and MMP-9 gene expression were upregulated by 4 and 3.4 folds respectively. Zymographic analysis found MMP activity only in 4T1B. Conclusion: These results offer significant information about the massive alteration of MMPs expression in the brain metastasis of TNBC. By analyzing the molecular characteristics of brain metastatic tumor cells, we can understand the molecular and genetic features of brain metastasis and develop tailored therapeutic strategies to combat TNBC brain metastasis.

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