Matrix metalloproteinase localisation by in situ-RT-PCR in archival human breast biopsy material.
Utilising archival human breast cancer biopsy material we examined the stromal/epithelial interactions of several matrix metalloproteinases (MMPs) using in situ-RT-PCR (IS-RT-PCR). In breast cancer, the stromal/epithelial interactions that occur, and the site of production of these proteases, are central to understanding their role in invasive and metastatic processes. We examined MT1-MMP (MMP-14, membrane type-1-MMP), MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) for their localisation profile in progressive breast cancer biopsy material (poorly differentiated invasive breast carcinoma (PDIBC), invasive breast carcinomas (IBC) and lymph node metastases (LNM)). Expression of MT1-MMP, MMP-1 and MMP-3 was observed in both the tumour epithelial and surrounding stromal cells in most tissue sections examined. MT1-MMP expression was predominantly localised to the tumour component in the pre-invasive lesions. MMP-1 gene expression was relatively well distributed between both tissue compartments, while MMP-3 demonstrated highest expression levels in the stromal tissue surrounding the epithelial tumour cells. The results demonstrate the ability to distinguish compartmental gene expression profiles using IS-RT-PCR. Further, we suggest a role for MT1-MMP in early tumour progression, expression of MMP-1 during metastasis and focal expression pattern of MMP-3 in areas of expansion. These expression profiles may provide markers for early breast cancer diagnoses and present potential therapeutic targets.
Genomics Research Centre, School of Medical Science, Griffith University Gold Coast, PMB 50 Gold Coast Mail Centre, Qld. 9726, Australia. lhaupt@imcb.a-star.edu.sg
Larisa M
LM
Haupt
Rachel E
RE
Irving
Stephen R
SR
Weinstein
Michael G
MG
Irving
Lyn R
LR
Griffiths
D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy / Q000379:methods*; D001940:Breast / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
D014408:Biomarkers, Tumor; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1; D053511:Matrix Metalloproteinase 14