prostate tumor

The Galectin family of proteins, with specificity for Nacetyllactosaminecontaining glycoproteins, consists of beta-galactoside binding lectins containing homologous carbohydrate recognition domains (CRDs). They also possess hemagglutination activity, which is attributable to their bivalent carbohydrate binding properties. Galectins are active both intracellularly and extracellularly. Although they are localized primarily in the cytoplasm and lack a classical signal peptide, galectins can also be secreted by one or more unidentified, non-classical, secretory pathways. They have diverse effects on many cellular functions including adhesion, migration, polarity, chemotaxis, proliferation, apoptosis, and differentiation. Galectins may therefore play a key role in many pathological states, including autoimmune diseases, allergic reactions, inflammation, tumor cell metastasis, atherosclerosis, and diabetic complications. The galectins have been classified into the prototype galectins(1, 2, 5, 7, 10, 11, 13, 14), which contain one CRD and exist either as a monomer or a noncovalent homodimer. The chimera galectins(Galectin3) containing one CRD linked to a nonlectin domain, and the tandemrepeat Galectins(4, 6, 8, 9, 12) consisting of two CRDs joined by a linker peptide.Galectins lack a classical signal peptide and can be localized to the cytosolic compartments where they have intracellular functions. However, via one or more as yet unidentified nonclassical secretory pathways, galectins can also be secreted to function extracellularly. Individual members of the galectin family have different tissue distribution profiles and exhibit subtle differences in their carbohydrate-binding specificities. Each family member may preferentially bind to a unique subset of cell surface glycoproteins.

Galectin-8 LGALS8 Protein, Human, Recombinant (GST) is expressed in E. coli expression system with N-GST tag. The predicted molecular weight is 62.8 kDa and the accession number is O00214.

B7 Homolog 4 (B7-H4) is glycosylated member of the B7 family of immune costimulatory proteins.It is widely expressed, including in kidney, liver, lung, pancreas, placenta, prostate, spleen, testis and thymus. B7-H4 negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. It also involved in promoting epithelial cell transformation.

TDGF1 (CRIPTO) is a member of the epidermal growth factor-Cripto-1 FRL-1 Cryptic (EGF CFC) gene family and an obligate co-receptor involved in NODAL signaling, a developmental program implicated in midline, forebrain, and left-right axis development in model organisms. Cripto-1 is enriched in a subpopulation of embryonal, melanoma, prostate, and pancreatic cancer cells that possess stem-like characteristics. Therefore, Cripto-1 may play a role during developmental EMT, and it may also be involved in the reprogramming of differentiated tumor cells into cancer stem cells through the induction of an EMT program.

GADD45G, also known as CR6, is part of the nuclear proteins to interact with various proteins whose transcript levels are raised after stressful growth arrest conditions and treatment with DNA-damaging agents. GADD45G reacts to environmental stresses by mediating activation of the p38 JNK pathway which is mediated through their protein binding and activating MTK1 MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. GADD45G acts as a new-age tumor suppressor however is being frequently inactivated epigenetically in multiple tumors. GADD45G mRNA expression is down-regulated in hepatocellular carcinoma. GADD45G causes cell cycle arrest at G2 M transition when transfected into Hep-G2 cells. GADD45G induction by androgens involves new protein synthesis. Overexpression of GADD45G inhibits cell growth and causes morphological modifications in prostate cell lines thus GADD45G takes part in differentiation induction by androgens.

Tumor protein p63 is a protein also known as transformation-related protein 63, TP63, and p63. Tumor protein p63 p63 is a member of the p53 family of transcription factors whose members P53, p63, and p73 have similar features in their gene structures and functions. An animal model, p63- - mice has been useful in difining the role p63 plays in the development and maintenance of stratified epithelial tissues. This p63 encoding protein p63 has a dramatic impact on replenishment of cutaneous epithelial stem cells and on ovarian germ cell survival. Although these two fundamental roles of p63 attest to its powerful place in development, its other functions, specifically the apparent capacity of p63, is to supervise the emergence of new cell populations in the breast, prostate, cervix, and upper reproductive tract. P63- - mice have several development defects which include the lack of limbs and other tissues, such as teeth and mammary glands, which develop as a result of interactions between mesenchyme and epithelium. Mutations in this protein are associated with ectodermal dysplasia, and cleft lip palate syndrome 3, ADULT syndrome (acro-dermato-ungual-lacrimal-tooth), limb-mammary syndrome, et al.

PCK2 promotes tumor initiation by lowering acetyl-CoA level through reducing the mitochondrial tricarboxylic acid (TCA) cycle. The levels of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) are critical for the metabolic switch and the maintenance of TICs in prostate cancer. PCK2 is a potential therapeutic target for aggressive prostate tumors.

CD254, also known as RANKL, TNFSF11, TRANCE, OPGL and ODF, is a type II membrane protein of the tumor necrosis factor (TNF) superfamily, and affects the immune system and control bone regeneration and remodeling. RANKL is the ligand of nuclear factor (NF)-κB (RANK). When RANKL binds to RANK, it will undergo trimerization and then bind to an adaptor molecule TNF receptor-associated factor 6 (TRAF6). This results in the activation of several downstream signaling cascades, including the NFκB, mitogen-activated protein kinases (MAPK), activating protein 1 (AP-1), and nuclear factor of activated T cells (NFATc1), resulting in the formation of multinucleated bone-resorbing osteoclasts. RANKL is widely expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoblast, mammary gland epithelial cells, prostate and pancreas.

Prolactin receptor (PRLR) is highly expressed in a subset of human breast cancer and prostate cancer, which makes it a potential target for cancer treatment. In clinical trials, the blockade of PRLR was shown to be safe but with poor efficacy. It is therefore urgent to develop new therapies against PRLR target. Bispecific antibodies (BsAbs) could guide immune cells toward tumor cells, and produced remarkable effects in some cancers. PRLR Protein, Canine, Recombinant (hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 53.89 kDa and the accession number is XM_038663941.1.

Erythropoietin‑producing hepatocellular carcinoma cell surface type‑A receptor 3 (EPHA3) has been found to promote the proliferation and survival of prostate cancer (PCa) cell lines and prostate tumor development in nude mice. The interaction of AR and SP1 contributes to regulate EPHA3 expression, and the SP1 binding sites (‑295~‑261) in the EPHA3 core promoter region is crucial to the regulation of EPHA3 expression in response to androgen hormone stimuli.

Monocyte chemoattractant protein 1 (MCP-1), also called CCL2, is a member of the beta (C-C) subfamily of chemokines that is a chemoattractant for monocytes and basophils but not eosinophils or neutrophils. CCL2 binds the cognate receptor CCR2, and together this signaling pair has been shown to have multiple pro-tumorigenic roles, from mediating tumor growth and angiogenesis to recruiting and usurping host stromal cells to support tumor progression. CCL2 is found in the circulation, where it has been suggested as a diagnostic biomarker of breast cancer and prostate cancer. CCL2 can also induce arachidonic acid release in human monocytes, which has been shown to be involved in adhesion and induction of the chemotactic response, in a pertussis-toxinsensitive manner.

B7 Homolog 4 (B7-H4) is glycosylated member of the B7 family of immune costimulatory proteins. Mature human B7-H4 consists of a 235 amino acid (aa) extracellular domain (ECD) with two Ig-like V-type domains, a 21 aa transmembrane segment, and a 2 aa cytoplasmic tail. It is widely expressed, including in kidney, liver, lung, pancreas, placenta, prostate, spleen, testis and thymus. B7-H4 negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. It also involved in promoting epithelial cell transformation.

Prolactin receptor (PRLR) is highly expressed in a subset of human breast cancer and prostate cancer, which makes it a potential target for cancer treatment. In clinical trials, the blockade of PRLR was shown to be safe but with poor efficacy. It is therefore urgent to develop new therapies against PRLR target. Bispecific antibodies (BsAbs) could guide immune cells toward tumor cells, and produced remarkable effects in some cancers. PRLR Protein, Cynomolgus, Recombinant (His) is expressed in HEK293 mammalian cells with C-His tag. The predicted molecular weight is 25.75 kDa and the accession number is A0A2K5WXK1.

Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue- and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid.

Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8) family is a newly identified protein with vital roles in maintaining immune homeostasis. Tumor necrosis factor-alpha-inducible protein 8 (TNFAIP8) is a TNF-alpha inducible anti-apoptotic protein with multiple roles in tumor growth and survival. by the creation of cellular autophagy events, TNFAIP8 promotes cell survival and drug resistance in prostate cancer cells. TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation and invasion in lung cancer. TNFAIP8 may serve as a candidate biomarker for poor prognosis and a target for new therapies.

Ephrins-A3 belongs the Ephrins ligand family which involved in a variety of biological processes, especially in the nervous system and in erythropoiesis. It is shown that Ephrin-A3 is expressed in brain, skeletal muscle, spleen, thymus, prostate, testis, ovary, small intestine, and peripheral blood leukocytes. Ephrin-A3 has a GPI anchor following the extracellular sequence and a signal sequence of 22 amino acids. Ephrin-A3 can bind EphA2, EphA3, EphA4, EphA5, EphA6, EphA7, EphA8 and EphB1. Futhermore, it is associated with tumor growth and metastasis.

Receptor Activator of Nuclear Factor κ B (RANK), also known as CD265, TRANCE Receptor or TNFRSF11A, is member of the tumor necrosis factor receptor (TNFR) molecular superfamily. RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK RANKL OPG signaling pathway that regulates osteoclast differentiation and activation. It plays a vital role in bone remodeling and repair, immune cell function, lymph node development, thermal regulation, and mammary gland development. RANK is constitutively expressed in skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, vascular cell, and pancreas.

Semaphorin 3C is one of six Class 3 secreted semaphorins, which are potent chemorepellents, that play a role in axon and or vascular guidance during development can be up-regulated in the process of tumor progression. Semaphorin 3C consists of a 20 amino acids signal sequence, a N-terminal Sema domain, a cysteine knot, a furine-type cleavage site, an Ig-like domain, and a C-terminal basic domain. Semaphorin 3C expressed highly in the heart, colon, skeletal muscle, small intestine, testis, ovary and prostate, expressed lowly in the other organs, including the brain.

Latexin, also known as endogenous carboxypeptidase inhibitor, tissue carboxypeptidase inhibitor, TCI, ECI, and LXN, is a cytoplasm protein that belongs to the protease inhibitor I47 (latexin) family. It is highly expressed in the heart, prostate, ovary, kidney, pancreas, and colon. Latexin LXN is the only known endogenous specific inhibitor of zinc-dependent metallocarboxypeptidases (MCPs) present in mammalians so far. Latexin is originally identified as a molecular marker for the regional specification of the neocortex in development in rats. The 222 amino acid latexin in the human shows different expression distribution with high levels in heart, prostate, ovary, kidney, pancreas, and colon, but only moderate or low levels in other tissues including the brain. Latexin is also expressed at high levels and is inducible in macrophages in concert with other protease inhibitors and potential protease targets, and thus is suggested to play a role in inflammation and innate immunity pathways. Despite the non-detectable sequence similarity with plant and parasite inhibitors, Latexin is related to a human putative tumor suppressor protein, TIG1. Also, Latexin is implicated in Alzheimer's disease.

ATP6V1F encodes a component of vacuolar ATPase mediating acidification. The cDNA and the genomic sequences of ATP6V1F were cloned successfully for the first time from the Giant Panda (Ailuropoda melanoleuca) using reverse transcription polymerase chain reaction and touchdown-polymerase chain reaction, respectively. Topology prediction showed that there is one protein kinase C phosphorylation site, two Casein kinase II phosphorylation sites, and one N-myristoylation site in the ATP6V1F protein. Up-regulated expression of mammary tumor 8 kDa protein (MAT-8), complement component C1S (C1S), ferritin heavy chain (FTH1), peptidyl-prolyl cis-trans isomerase A (PPIA), RNA-binding protein regulatory subunit DJ-1 protein (DJ-1) and vacuolar ATP synthase subunit F (ATP6V1F) was determined in prostate carcinoma and confirmed by using quantitative real-time RT-PCR analyses.

Serine Protease Inhibitor Kazal-Type 1 (SPINK1) is a trypsin inhibitor that prevent the trypsin-catalyzed premature activation of zymogens within the pancreas. Defects in SPINK1 are a cause of pancreatitis (PCTT). A disease characterized by the presence of calculi in pancreatic ducts. It causes severe abdominal pain attacks. Defects in SPINK1 are the cause of susceptibility to tropical calcific pancreatitis (TCP). Recombinant SPINK1 protein (rSPINK1) stimulated cell proliferation in benign RWPE as well as cancerous prostate cells. The research result indicated that the potential of SPINK1 as an extracellular therapeutic target in prostate cancer. In contrast, knockdown of SPINK1 in 22RV1 cells inhibited cell proliferation, cell invasion, and tumor growth in xenograft assays.

Olfactomedin-4, also known as G-CSF-stimulated clone 1 protein, Antiapoptotic protein GW112, and OLFM4, is a secreted protein that contains one olfactomedin-like domain. The OLFM4 gene was recently reported to inhibit various apoptotic pathways and promote the proliferation of cancer cells, suggesting that OLFM4 might serve as a diagnostic marker for human cancers. Thus, OLFM4 mRNA might be a useful tool to support the diagnosis of cancer, irrespective of the clinical stages. It is overexpressed in some human tumor types, especially in those of the digestive system. GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis. Functionally, GW112 could significantly attenuate the ability of GRIM19 to mediate retinoic acid-IFN-beta-mediated cellular apoptosis and apoptosis-related gene expression. Also, GW112 demonstrated strong antiapoptotic effects in tumor cells treated with other stress exposures such as hydrogen peroxide. Finally, forced overexpression of GW112 in murine prostate tumor cells led to more rapid tumor formation in a syngeneic host. OLFM4 is an important regulator of cell death that plays important roles in tumor cell survival and tumor growth. As a candidate gene for cancer-specific expression. The serum olfactomedin 4 (OLFM4) is a useful marker for Gastric cancer (GC) and its measurement alone or in combination with Reg IV has utility in the early detection of GC. GW112 has an antiapoptotic property against the cytotoxic agents-induced apoptosis. It suggested that GW112 could be an important mediator in NF kappaB-dependent tumorigenesis of digestive tract tissues.

Poly(rC)-binding protein 1, also known as Heterogeneous nuclear ribonucleoprotein E1, Alpha-CP1, Nucleic acid-binding protein SUB2.3 and PCBP1, is a family member of heterogeneous nuclear ribonucleoproteins (hnRNPs) that belong to RNA-binding proteins and bear three KH domains. PCBP1 is loosely bound in the nucleus. It may shuttle between the nucleus and the cytoplasm. It is abundantly expressed in skeletal muscle, thymus and peripheral blood leukocytes while a lower expression is observed in prostate, spleen, testis, ovary, small intestine, heart, liver, adrenal and thyroid glands. PCBP1 is widely expressed in many human tissues and involved in the regulation of transcription, transportation process, and function of RNA molecules. PCBP1 plays a pivotal role in post-transcriptional regulation for RNA metabolism and RNA function in gene expression. PCBP1 acts as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.

The growth arrest-specific 6 gene (GAS6) is a member of the family of plasma vitamin K-dependent proteins, which are able to bind to phospholipids using an N-terminal gamma-carboxyglutamic acid domain. GAS6 is a vitamin K-dependent protein, plays a role in the survival, proliferation, migration, differentiation, adhesion, and apoptosis of cells. The growth arrest-specific 6 (GAS6) has been implicated in systemic inflammation and coagulation. Growth arrest-specific 6 (GAS6), plays a role in tumor progression by regulating growth in many cancers. GAS6, expressed by osteoblasts in the bone marrow, plays a significant role in the regulation of PCa cell survival during chemotherapy, which will have important implications for targeting metastatic disease. The GAS6 TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. It had been show that GAS6 signaling regulates invasion, proliferation, chemotherapy-induced apoptosis of prostate cancer (PCa) cells, and GAS6 secreted from osteoblasts in the bone marrow environment plays a critical role in establishing prostate tumor cell dormancy.