Expression of migration stimulating factor in breast tissues and its clinical significance

Introduction

Migration stimulating factor (MSF) is a novel angiogenic factor previously identified in breast tumours and their associated stroma. The aim of this study was to determine the possible diagnostic and prognostic value of MSF expression in these tumours and its effects on breast-derived cells in vitro.

Methods

Paraffin-embedded archival breast tissues were stained with specific MSF antibodies and the level of staining was semiquantified either by consensus of two or three independent observers or by computer-assisted image analysis. The effects of rhMSF on the migration and proliferation of breast carcinoma cells, fibroblasts and endothelial cells were examined in tissue culture.

Results

MSF expression was generally low or negligible in normal breast tissue derived from reduction mammoplasties (NB; n = 19). However, histologically normal breast from the resection margin of breast tumours (NB-T; n = 17) showed significantly higher expression than NB. Significant increases in MSF expression were also observed from NB to benign lesions (B; n = 8) and from any of these tissues (B, NB or NB-T) to malignant tumours (T; n = 23), whereas B and NB-T showed similar expression.

MSF was detected in approximately 85% of the tumours examined, being heterogeneously expressed in carcinoma cells as well as in fibroblasts and blood vessels. In a cohort of 71 tumours, high MSF expression was associated with larger tumour size and shorter patient overall survival. Stromal MSF produced the most significant results. Recombinant MSF stimulated the migration, but not the proliferation, of breast carcinoma cells, fibroblast and endothelial cells.

Conclusions

This study indicates that MSF expression is associated with breast tumour development and aggressiveness. Besides inducing angiogenesis, MSF acts as an autocrine and paracrine motogen in breast tissues.