Expression of metastasis suppressor gene maspin in breast cancer brain metastases

Abstract

20057 Background: Recently our demonstrated that the expression of several Metastasis Suppressor Genes (MSG) is reduced in breast cancer brain metastases. Current data suggest that MSG Maspin (serpin B5) is a promising candidate for further treatment options. So, we examined the mRNA and protein expression of Maspin in normal breast tissue, breast cancer primaries, -brain metastases and breast cancer cell lines. Methods: Maspin mRNA expression was examined by real time reverse transcription polymerase chain reaction (RT-PCR) in fresh frozen samples from normal breast tissue, breast cancer primaries and -brain metastases. Furthermore maspin was examined in poorly invasive and non-metastatic breast cancer cell lines MCF-7, T47-D, in highly invasive and metastatic MDA-MB-231 breast cancer cells (231-parental) and in brain- and bone-selective metastatic clones (231-brain, 231-bone). Maspin protein was detected by immunohistochemistry in paraffin-embedded sections from 16 patients with breast cancer primaries and brain metastases using a specific monoclonal mouse antibody. Results: In relation to normal breast tissue, maspin mRNA expression was decreased in primary tumors and again decreased in brain metastases. Normalized ΔCT values were 1 (normal tissue), 0.3 (primary tumors) and 0.13 (brain metastases). Immunohistochemistry revealed the same tendency. 3 of 16 (19%) breast cancer primaries were positive whereas none of the brain metastases showed positive maspin staining. In comparison to poorly invasive breast cancer cell lines, maspin mRNA expression was decreased in 231-parental, increased in 231-brain and not detectable in 231-bone. Conclusions: Maspin expression is reduced in breast cancer brain metastases. It is differentially expressed in brain- and bone-selective metastatic cell lines. These results suggest an important role for maspin in breast cancer brain metastasis. No significant financial relationships to disclose.