ns expressed by EVT whereas treatment with non-decidualized CM was associated with an increase in the number of proteases expressed by EVT. A recent study showed CECAM1 expression 
by AC1M88 spheriods is enhanced following co-culture with decidualized HESC, however to our knowledge this is the first study to suggest that non-decidualized factors regulate protease expression by EVTs. The EVT proteins identified here included secreted proteins and cell surface proteins. We expected to find cell surface proteins in our CM as our methodology did not exclude cell debris or exosomes given the likely importance of membrane proteins in the regulation of trophoblast invasion. While proteomic analysis of purified EVT plasma membrane would be ideal, we were limited by cell number; isolating purified plasma membrane from primary EVT requires a prohibitively large number of cells. The decidualization CM used in this study was chosen to reflect the degree of decidualization found in HESC during the 1st trimester; when EVT invade through the decidua and into the top 3rd of the myometrium. Decidual biopsies from weeks 810 of gestation secrete 0.3 mIU/mg prolactin in 24 h. Here, prolactin secretion was 3.1 mIU/mg over 48 h, however it should be noted that this was from a purified population of HESC; in a decidual biopsy, less than 50% of the tissue is decidual cells; the tissue includes leukocytes, endothelial cells, smooth muscle and connective tissue. To standardize the degree of decidualization we also excluded under- and over-decidualized CM. Profilin 1 is an G-actin-binding protein which regulates actin dynamics on the plasma membrane by regulating actin polymerization. Profilin 1 is critical for order Lck Inhibitor normal cell proliferation and differentiation and is vital for actin-based cell motility, cytokinesis, neuronal differentiation and regulation of membrane trafficking and nuclear transport. Here, decidualized PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22189790 CM up-regulated profilin 1 levels in EVT CM, suggesting that decidualized CM induced profilin 1 secretion. Profilin 1 Decidual Factors Alter Trophoblast Proteins secretion by mesenchymal stem cells increases during ionizing radiation induced senescence. In vivo, EVT are nonproliferative; perhaps decidual factors induce senescence in EVT. Certainly, profilin 1 is thought to be a tumor suppressor: it is downregulated in aggressive forms of cancer compared to normal cells and inhibits cell functions required for metastasis including proliferation and migration. EVT are also highly motile and as an actin-binding protein, profilin 1 regulates cell motility, however the exact function of profilin 1 in the regulation of motility is not clear. Although profilin 1 inhibits migration in breast cancer cells, profilin 1 stimulates migration of HUVEC and mesenchymal stem cells and is enriched at the dynamic plasma membranes of migrating or spreading cells. It remains to be determined how the up-regulation of profilin 1 induced by decidualized CM modulates EVT function; the literature currently suggests profilin 1 regulates motility differently between cancerous and normal cells. Annexin A2 is a calcium-dependent phospholipid binding protein which is present in intracellular, membrane and secreted forms. It has roles in membrane fusion and signal transduction and is over-expressed in a variety of cancers. Secreted and surface annexin A2 interacts with cell matrix and proteases to regulate cell migration and adhesion and it is involved in macrophage activation. Induc