Platelet-Activating Factor Acetylhydrolase (PAFAH) is a secreted enzyme which belongs to the AB hydrolase superfamily and Lipase family and catalyzes the degradation of platelet-activating factor to biologically inactive products. PAFAH is produced by inflammatory cells and hydrolyzes oxidised phospholipids in LDL. PAFAH has been implicated in the development of atherosclerosis and has also been identified as a marker for cardiac disease. PAFAH might have a major physiologic effect in the presence of inflammatory bodily responses. PAFAH alters the action of PAF by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. PAFAH has specificity for substrates with a short residue at the sn-2 position.
Placental growth factor is a protein that in humans is encoded by the PGF gene. It is a secreted protein and belongs to the PDGF/VEGF growth factor family. Alternate splicing results in at least three human mature PlGF forms containing 131 (PlGF-1), 152 (PlGF-2), and 203 (PlGF-3) amino acids (aa) respectively. PlGF is mainly found as a variably glycosylated, secreted, 55-60 kDa disulfide linked homodimer.The protein is a member of the VEGF (vascular endothelial growth factor) sub-family-a key molecule in angiogenesis and vasculogenesis, in particular during embryogenesis. The main source of PGF during pregnancy is the placental trophoblast. PGF is also expressed in many other tissues, including the villous trophoblast. PlGF (especially PlGF-1) and some forms of VEGF can form dimers that decrease the angiogenic effect of VEGF on VEGF R2. PlGF-2, like VEGF164/165, shows heparin-dependent binding of neuropilin (Npn)-1 and Npn-2, and can inhibit nerve growth cone collapse. Circulating PlGF often correlates with tumor stage and aggressiveness, and therapeutic PlGF-2 antibodies are being investigated for their ability to inhibit tumor growth and angiogenesis.
ALPP is a membrane protein and exits as a homodimer. ALPP is expressed only in normal term placenta, endocervix and fallopian tube and also in ovarian and proximal gastrointestinal tumors. It has been shown to play a role in a number of processes including cell signaling, long-term potentiation, and cell adhesion, however, the best known and most commonly studied role is implicated in Alzheimer's research.
Chorionic Somatomammotropin Hormone (CSH1) belongs to the Somatotropin/Prolactin family. It is located at the growth hormone locus on chromosome 17. It is produced by cells in the syncytiotrophoblast layer of the placenta only during pregnancy. Although CSH1 does not interact with GHR but only activates PRLR through zinc-induced dimerization. It is expressed mainly in the placenta and utilizes multiple transcription initiation sites. CSH1 plays an important role in stimulating lactation, growth control and metabolism.
Platelet Glycoprotein 4 (CD36) is an integral membrane glycoprotein that has multiple physiological functions. It is broadly expressed on a variety of cell types including microvascular endothelium, adipocytes, skeletal muscle, epithelial cells of the retina, breast, and intestine, smooth muscle cells, erythroid precursors, platelets, megakaryocytes, dendritic cells, monocytes/macrophages, and microglia. As a member of the scavenger receptor family, CD36 is a multiligand pattern recognition receptor that interacts with a large number of structurally dissimilar ligands, including long chain fatty acid (LCFA), advanced glycation end products (AGE), thrombospondin-1,oxidized lowdensity lipoproteins (oxLDLs), high density lipoprotein (HDL), phosphatidylserine, apoptotic cells, β amyloid fibrils (fAβ), collagens I and IV, and Plasmodium falciparuminfected erythrocytes. CD36 is required for the antiangiogenic effects of thrombospondin-1 in the corneal neovascularization assay. It plays a role in lipid metabolism and has been identified as a fatty acid translocase necessary for the binding and transport of LCFA in cells and tissues.
Urokinase plasminogen activator (uPA) and/or its receptor (uPAR) are essential for metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumours. uPAR and uPA levels in both resected tumor tissue and plasma are of independent prognostic significance for patient survival in several types of human cancer. This system has classically been thoμght to drive tumor progression by mediating directed extracellular proteolysis on the surface of migrating or invading cells, and intervening with this proteolysis by targeting uPAR has been proposed to represent a novel approach for inhibiting tumor progression. uPAR, also known as PLAUR or CD87, has been implicated in the growth, metastasis, and angiogenesis of several solid and hemotologic malignancies. uPAR is a highly glycosylated, 55-60 KD integral membrane protein linked to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. It is part of a cell surface system that also consists of the serine protease uPA and several specific inhibitors (plasminogen activator inhibitors 1 and 2). Additionally, the analysis of CD87 (urokinase-type plasminogen activator receptor-uPAR) expression has a potential role in the diagnostic or prognostic work-up of several hematological malignancies, particularly acute leukemia and multiple myeloma.
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