Spontaneous metastasis in matrix metalloproteinase 3-deficient mice.
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.
Juncker-Jensen
Anna
A
Finsen Laboratory, Rigshospitalet, Copenhagen Biocenter, Copenhagen N, Denmark.
Rømer
John
J
Pennington
Caroline J
CJ
Lund
Leif R
LR
Almholt
Kasper
K
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006868:Hydrolysis; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; D019278:Matrix Metalloproteinase 3