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Updated: Jun 27, 2026
An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis
Published on: August 14, 2016
Spontaneous metastasis in matrix metalloproteinase 3-deficient mice
Anna Juncker-Jensen1, John Rømer, Caroline J Pennington
1Finsen Laboratory, Rigshospitalet, Copenhagen Biocenter, Copenhagen N, Denmark.
Abstract:
Matrix metalloproteinases (MMPs) have been linked to the metastatic potential of tumor cells due to their ability to degrade the extracellular matrix. MMP-3 (stromelysin-1) is upregulated in a wide variety of human tumors. We used the MMTV-PyMT breast cancer model to determine if MMP-3 is involved in tumorigenesis and metastatic growth. In this model the stromal expression of MMP-3 mRNA resembles the predominant MMP-3 expression pattern observed in human ductal breast carcinomas. We studied a cohort of 63 PyMT transgenic mice, either deficient for MMP-3 or wild-type controls. The degree of metastasis did not differ significantly between the two groups of mice, although the median lung metastasis volume was more than threefold increased in MMTV-PyMT mice deficient in MMP-3. Likewise, primary tumor growth rate and lymph node metastasis were not significantly affected by MMP-3-deficiency. By comparing mRNA levels in MMP-3-deficient PyMT tumors with PyMT wild-type tumors we excluded compensatory transcriptional changes of other MMPs or their specific inhibitors. Thus, we conclude that genetic ablation of MMP-3 does not significantly affect tumor growth and metastasis in the MMTV-PyMT model.
Insights
Matrix metalloproteinase-3 (MMP-3) deficiency did not significantly alter tumor growth or metastasis in a mouse model. However, MMP-3-deficient mice showed increased lung metastasis volume, suggesting a complex role in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) degrade extracellular matrix, influencing tumor cell metastasis.
- MMP-3 (stromelysin-1) is frequently upregulated in human cancers.
- The MMTV-PyMT mouse model mimics human breast cancer progression.
Purpose of the Study:
- To investigate the role of MMP-3 in tumorigenesis and metastatic growth using the MMTV-PyMT mouse model.
- To assess the impact of MMP-3 deficiency on primary tumor growth, lymph node metastasis, and lung metastasis.
Main Methods:
- Studied 63 PyMT transgenic mice, comparing MMP-3 deficient and wild-type groups.
- Analyzed primary tumor growth rate, lymph node metastasis, and lung metastasis volume.
- Compared mRNA levels of MMPs and inhibitors in deficient versus wild-type tumors to rule out compensatory changes.
Main Results:
- No significant difference in the overall degree of metastasis between MMP-3 deficient and wild-type mice.
- Median lung metastasis volume was over threefold greater in MMP-3 deficient MMTV-PyMT mice.
- Primary tumor growth and lymph node metastasis were not significantly affected by MMP-3 deficiency.
Conclusions:
- Genetic ablation of MMP-3 does not significantly impact overall tumor growth and metastasis in the MMTV-PyMT model.
- Despite no change in overall metastasis, MMP-3 deficiency led to increased lung metastasis volume, indicating a nuanced role.
