Related Experiment Video
Updated: Jan 5, 2026
The Use of Mouse Mammary Tumor Cells in an In Vitro Invasion Assay as a Measure of Oncogenic Cell Behavior
Published on: June 12, 2019
Involvement of matrix metalloproteinase activity in hormone-induced mammary tumor regression
Marina Simian1, Alfredo Molinolo, Claudia Lanari
1Laboratorio de Carcinogénesis Hormonal, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. marina.simian@galuzzi.com
Abstract:
Proteolytic activity and remodeling of the extracellular matrix are important players in tumor progression. However, to date the role of the extracellular matrix in tumor regression remains unresolved. To address this, we used a progesterone-dependent in vivo mouse mammary tumor line, C4-HD, which regresses in response to hormone therapy. Within the first 72 hours of treatment, massive apoptosis was accompanied by changes in the staining patterns of laminin and collagens I, III, and IV. We thus hypothesized that an increase in matrix metalloproteinase (MMP) activity could be involved in this process. This indeed was the case as the activities of MMP-2, -9, and -3 increased in regressing tumors, coinciding with the peak of apoptosis. Moreover, cell-cell interactions were disrupted during early hours of regression with E-cadherin levels reduced and fragmentation products detected during regression. Analysis of beta-catenin revealed that although total levels within the tissue did not change, this molecule switched from being involved in cell-cell adhesion in the growing tumor to being expressed in the reactive stroma during regression. Our data provide a novel role for proteolytic activity in tumor regression and question the underlying principle for using MMP inhibitors in cancer treatment.
Insights
Matrix metalloproteinase (MMP) activity increases during tumor regression, challenging the use of MMP inhibitors in cancer treatment. This study reveals a novel role for proteolysis in tumor regression.
Area of Science:
- Oncology
- Biochemistry
- Cell Biology
Background:
- Extracellular matrix remodeling and proteolytic activity are key in tumor progression.
- The role of the extracellular matrix in tumor regression is not well understood.
Purpose of the Study:
- To investigate the role of extracellular matrix remodeling and matrix metalloproteinase (MMP) activity during tumor regression.
- To elucidate the mechanisms underlying hormone-induced tumor regression in a mouse model.
Main Methods:
- Utilized a progesterone-dependent mouse mammary tumor line (C4-HD) that undergoes regression upon hormone therapy.
- Analyzed changes in extracellular matrix components (laminin, collagens I, III, IV) and MMP activity (MMP-2, -9, -3) during regression.
- Assessed cell-cell adhesion molecules (E-cadherin, beta-catenin) and their localization during tumor regression.
Main Results:
- Massive apoptosis and significant changes in extracellular matrix composition were observed within 72 hours of treatment.
- Increased activity of MMP-2, MMP-9, and MMP-3 correlated with the peak of apoptosis during tumor regression.
- Disruption of cell-cell interactions, reduced E-cadherin levels, and altered beta-catenin localization were noted during early regression.
Conclusions:
- Proteolytic activity, specifically increased MMP activity, plays a significant role in tumor regression.
- The findings question the therapeutic strategy of using matrix metalloproteinase inhibitors for cancer treatment.
- This study highlights a novel mechanism of tumor regression involving extracellular matrix remodeling and proteolytic enzymes.
Related Concept Videos
01:23Role of Matrix Metalloproteases in Degradation of ECM
02:17The Tumor Microenvironment