Disease relevance of CRISP3

• Cysteine-rich secretory protein-3: a potential biomarker for prostate cancer [1].
• In situ hybridization experiments indicated that CRISP-3 mRNA is epithelial-specific and is up-regulated in prostate adenocarcinoma compared with benign prostate tissue [1].
• High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP [2].
• Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis [2].
• Characterization of the cysteine-rich secretory protein 3 gene as an early-transcribed gene with a putative role in the pathophysiology of Sjögren's syndrome [3].
• Further research should aim to elucidate the functions of CRISP-3 and MSP in prostate cancer cells [4].

High impact information on CRISP3

• In addition to previously described genes such as hepsin, overexpression of several genes was found that has not drawn attention before, such as the genes encoding the specific granule protein (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)-phospholipase A2, and the anti-apoptotic gene PYCR1 [5].
• In an attempt to interpret the expression of CRISP-3, normal peripheral blood lymphocytes (PBLs) were activated in vitro at different time points and assayed for CRISP-3 expression [3].
• Finally, B cells were transfected with the coding region of CRISP-3 and monitored for the up-regulation of different B cell activation markers [3].
• In addition, CRISP-3 was detected by RT-PCR between 30 minutes and 6 hours in phorbol myristate acetate-activated normal PBLs, while staurosporine inhibited this expression [3].
• The function of MSP is not known, but a recent study has shown MSP to bind CRISP-3, a protein present in neutrophilic granulocytes [6].

Chemical compound and disease context of CRISP3

• Interstitial and granuloma associated macrophages and giant cells contained partly undigested, immunoreactive SGP28-, vWF- and tryptase-positive cell rests and collagenous matrix [7].

Biological context of CRISP3

• Human CRISP-3 is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity [8].
• In transient transfection studies, CRISP-3 was found to be a secretory protein [1].
• Electronic profiling of publicly available expressed sequence tag databases identified a gene, cysteine-rich secretoryprotein-3 (CRISP-3), that is up-regulated in prostate cancer, and of which the expression is relatively prostate-specific [1].

Anatomical context of CRISP3

• We were able to show that human CRISP-3 is a quantitatively minor seminal plasma protein not associated with prostasomes [9].
• Furthermore, CRISP-3 expression was found in the secretory epithelium throughout the male genital tract, with particularly high expression in the cauda epididymis and ampulla vas deferens [9].
• SGP28 was originally discovered in human neutrophils, but transcripts are widely distributed in exocrine glands (salivary glands, pancreas, and prostate) and also found at lower levels in epididymis, ovary, thymus, and colon [10].
• Similarities to pathogenesis-related proteins in plants and the expression in neutrophils and exocrine glands suggest that SGP28/CRISP-3 may play a role in innate host defense [10].
• The presence of CRISP-3 in peroxidase-negative granules of neutrophils, in granules of eosinophils, and in exocrine secretions indicates a role in the innate host defense [11].

Associations of CRISP3 with chemical compounds

• In the context of the CRISP promoters a 2-fold induction by R1881 was measured for the CRISP-3 upstream region whereas only limited effects were noted for the CRISP-1 upstream region [12].
• It displays all 16 conserved cysteine residues and shows 82% homology to human and 78% to guinea pig CRISP-2 (AA1, TPX 1) and 77% to human CRISP-3 [13].

Other interactions of CRISP3

• The A1BG-CRISP-3 complex is noncovalent with a 1:1 stoichiometry and is held together by strong electrostatic forces [8].
• Rodents express only 2 CRISPs (CRISP-1 and CRISP-2) in their male reproductive system, whereas humans and horses express an additional third member named CRISP-3 [9].
• On the basis of the relatively high content of CRISP-3 in human plasma and the small size of the protein (28 kDa), we hypothesized that CRISP-3 in plasma was bound to another component [8].
• An ELISA for SGP28/CRISP-3, a cysteine-rich secretory protein in human neutrophils, plasma, and exocrine secretions [10].
• Due to far higher abundance of MSP in prostatic fluid, it manifests large overcapacity for CRISP-3 binding [14].

Analytical, diagnostic and therapeutic context of CRISP3

• We demonstrate that CRISP-3 is a specific and high-affinity ligand of A1BG with a dissociation constant in the nanomolar range as evidenced by surface plasmon resonance [8].
• To characterize the protein in seminal plasma and localize the production of CRISP-3 in the human male reproductive tract, we performed immunoblotting and enzyme-linked immunosorbent assay measurements of seminal plasma and immunohistochemistry and in situ hybridization of tissue specimens [9].
• We present a specific, accurate, and reproducible enzyme-linked immunosorbant assay (ELISA) for the measurement of CRISP-3 with a detection limit of 2 ng/ml [10].
• To investigate the subcellular localization and mobilization of CRISP-3 in human neutrophils, we performed subcellular fractionation of resting and activated neutrophils on three-layer Percoll density gradients, release-studies of granule proteins in response to different secretagogues, and double-labeling immunogold electron microscopy [11].
• CRISP-3 mRNA overexpression in cancer was confirmed using quantitative real-time reverse-transcription-PCR using benign prostatic epithelia and adenocarcinoma (in 5 of 5 cases) isolated by laser capture microdissection, as well as bulk tissues (in 20 of 23 cases) from surgically resected human prostates [1].

References