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Updated: Jun 7, 2026
Zebrafish Model of Neuroblastoma Metastasis
Published on: March 14, 2021
Matrix metalloproteinase-9 and cell division in neuroblastoma cells and bone marrow macrophages
M Gloria Sans-Fons1, Sonia Sole, Coral Sanfeliu
1Department of Brain Ischemia and Neurodegeneration, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Científicas, Institut d’Investigacions Biomèdiques August Pi i Sunyer, E-08036, Barcelona, Spain.
Abstract:
Matrix metalloproteinases (MMPs) degrade the extracellular matrix and carry out key functions in cell development, cancer, injury, and regeneration. In addition to its well recognized extracellular action, functional intracellular MMP activity under certain conditions is supported by increasing evidence. In this study, we observed higher gelatinase activity by in situ zymography and increased MMP-9 immunoreactivity in human neuroblastoma cells and in bone marrow macrophages undergoing mitosis compared with resting cells. We studied the pattern of immunoreactivity at the different stages of cell division by confocal microscopy. Immunostaining with different monoclonal antibodies against MMP-9 revealed a precise, dynamic, and well orchestrated localization of MMP-9 at the different stages of cell division. The cellular distribution of MMP-9 staining was studied in relation to that of microtubules. The spatial pattern of MMP-9 immunoreactivity suggested some participation in both the reorganization of the nuclear content and the process of chromatid segmentation. We then used several MMP-9 inhibitors to find out whether MMP-9 might be involved in the cell cycle. These drugs impaired the entry of cells into mitosis, as revealed by flow cytometry, and reduced cell culture growth. In addition, the silencing of MMP-9 expression with small interfering RNA also reduced cell growth. Taken together, these results suggest that intracellular MMP-9 is involved in the process of cell division in neuroblastoma cells and in primary cultures of macrophages.
Insights
Intracellular Matrix Metalloproteinase-9 (MMP-9) plays a crucial role in cell division. Inhibiting or silencing MMP-9 significantly reduces cell growth and impairs mitosis in neuroblastoma cells and macrophages.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are enzymes primarily known for their extracellular roles in matrix degradation.
- Emerging evidence suggests intracellular functions for MMPs under specific conditions.
- MMP-9's role in cell division has not been fully elucidated.
Purpose of the Study:
- To investigate the intracellular role of MMP-9 during cell division.
- To determine the localization and function of MMP-9 in dividing neuroblastoma cells and macrophages.
Main Methods:
- In situ zymography and confocal microscopy were used to assess gelatinase activity and MMP-9 localization.
- Immunostaining with specific antibodies mapped MMP-9 distribution during cell division stages.
- MMP-9 inhibitors and small interfering RNA (siRNA) were employed to assess functional impact.
Main Results:
- Elevated gelatinase activity and MMP-9 immunoreactivity were observed in mitotic cells compared to resting cells.
- MMP-9 exhibited precise, dynamic localization during different stages of cell division, correlating with microtubule distribution.
- MMP-9 inhibition or silencing led to impaired entry into mitosis and reduced cell growth.
Conclusions:
- Intracellular MMP-9 is dynamically localized and functionally involved in cell division processes, including nuclear reorganization and chromatid segmentation.
- MMP-9 activity is essential for normal cell cycle progression in neuroblastoma cells and macrophages.
- These findings highlight a novel intracellular role for MMP-9 in cell proliferation.
