Secretion of prosaposin, a multifunctional protein, by breast cancer cells

Western blotting and immunodetection with three antibodies were used to pro be conditioned media of breast cancer cells (MDA231 MDA435, MCF-7) for pros aposin, a lysosomal protein that occurs in milk. It was readily detected in media from these cells, and from that of an sv40-transformed mammary epith elial cell, HBL100, but not from medium of human neural tumor cells (SK-N-M C). In cultures of MCF-7 cells, the prosaposin pattern of secretion over ti me closely resembled that of procathepsin D, another lysosomal protein occu rring in milk. Supplementing medium with 17 beta-estradiol (0.1-100 nM) dos e dependently increased secretion of both proteins after 48 h without chang es in cell viability. The influence of 17 beta-estradiol on secretion could play a role in the trophic activity of prosaposin in cellular differentiat ion and cell death protection. In concert with other lysosomal proteins in the tumor environment, such as procathepsin D, prosaposin may be a factor i n eliminating barriers to tumor metastasis by facilitating hydrolysis of me mbrane glycolipids, The number of milk proteins known to be secreted by bre ast cancer cells is growing. There is evidence that at least some of these may be secreted in an endocrine manner in the normal, non-lactating breast. (C) 1999 Elsevier Science B.V. All rights reserved.