Expression Profile of Matrix Metalloproteinases in Primary and Metastatic Breast Cancer
M Tretiakova, NV Kaverina, P Pytel, ZG Kadagidze, AY Baryshnikov, IV Ulasov, MS Lesniak. University of Chicago, Chicago; NN Blokhin Russian Oncology Center, Moscow, Russian Federation
Background: Matrix metalloproteinases (MMP) are proteolytic enzymes degrading extracellular matrix components and playing crucial role in cancer development, progression and metastasis. The objective of this study was to determine mRNA and protein expression levels of collagenases MMP1, 2, and 9 in invasive ductal carcinoma (IDC) of breast, and their correlation with developing regional and distant brain metastases.
Design: mRNA levels of MMP were quantified by real-time RT-PCR in 12 frozen specimens including 4 primary IDC, 4 brain metastases and 4 normal breasts (NB), as well as in 6 human breast cancer cells lines, including IDC, and 1 subline, established from nude mice IDC brain metastasis. Tissue microarrays included 22 primary IDC, 17 brain metastasis (including 5 matched with primary), 5 lymph node metastasis (all matched), and 5 NB tissues. MMP protein expression levels were examined by immunostaining, quantified using automated imaging system (ACIS) and analyzed as integrated optical density (IOD) of brown staining per 10 mkm2.
Results: Human breast cancer cell lines demonstrated elevated mRNA levels of all studied MMP. Frozen tissues showed only MMP9 mRNA overexpression with trends of higher mRNA levels in IDC compared to NB or brain metastases. Immunostaining of primary and metastatic breast cancers also showed significant differential expression for MMP9. In brain metastases protein expression was present in 4/17 cases for MMP1, 1/17 for MMP2 and 15/17 cases for MMP9 (Anova p-values 0.91, 0.78 and 0.031 respectively). MMP9 IOD was higher in lymph node metastases vs IDC (p=0.024), and brain metastases vs primary IDC (p=0.01). It trended higher in IDC vs NB (p=0.056). We found strong positive correlation between MMP9 IOD in lymph node and brain metastases (p<0.05).
Conclusions: Enhanced MMP9 expression in metastatic breast cancer vs primary and normal breast tissue was found at both mRNA and protein levels. Our findings suggest that MMP9 may play significant role in aggressive behavior of breast cancer associated with local and brain metastases.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 6, Wednesday Afternoon