MMP-9 secretion and MMP-2 activation distinguish invasive and metastatic sublines of a mouse mammary carcinoma system showing epithelial-mesenchymal transition traits.
We have investigated the gelatinase profiles and invasiveness of clonal tumour sublines derived from a spontaneously arising mammary tumour in a Balb/cfC3H mouse. The 67NR. 66c14 and 4T1.2 sublines have low, intermediate and high metastatic potential respectively. In Boyden chamber studies, Matrigel invasion was seen to be progressively higher in the more metastatic lines 4T1.2>66c14>67NR, consistent with MMP-2 activation potential, MMP-9 secretion, and migration over either type I or IV collagen, which were low in both 67NR and 66c14 cells compared to 4T1.2 cells. These attributes are consistent with those seen in human breast cancer cell lines which appear to have undergone an epithelial-mesenchymal transition (EMT) as indicated by vimentin expression. We were, however, surprised to find vimentin expression, MT1-MMP expression and stellate Matrigel outgrowth in the non-invasive, non-metastatic 67NR cells. indicating that they had undergone an EMT despite not being invasive. We conclude that the EMT is manifested to differing degrees in these three clonal cell lines, and that the 67NR cells have either undergone a partial EMT or have since lost certain important attributes of the EMT-derived phenotype. This model should prove useful in further characterizing the regulation of MTI-MMP mediated MMP-2 activation and delineating the EMT in breast cancer progression.
Tester
A M
AM
VBCRC Breast Cancer Invasion and Metastasis Unit, St Vincent's Institute of Medical Research, Fitzroy, Australia.
Ruangpanit
N
N
Anderson
R L
RL
Thompson
E W
EW
D000818:Animals; D002465:Cell Movement; D004789:Enzyme Activation; D004848:Epithelium / Q000254:growth & development; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology*; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008648:Mesoderm / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000378:metabolism
C507096:Mmp14 protein, mouse; D014746:Vimentin; D019716:Tissue Inhibitor of Metalloproteinase-2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14