AbstractMatrix 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. © 2008 Wiley‐Liss, Inc.