HPSE Gene Editing

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HPSE Gene Editing    

HPSE (heparanase), also known as heparinase-1 (HPA1), is an endo-β-d-glucuronidase enzyme and acts on the cell surface and in the extracellular matrix to degrade long oligosaccharides polymerized heparan sulfate (HS) molecules into shorter chains (Figure 1). The expression of HSPE is tissue-specific, highly expressed in the placenta and spleen, and weakly expressed in lymph nodes, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver, and tumor tissues, and is also expressed in hair follicles. Proheparanase interacts with the cell membrane HS proteoglycan (HSPG) through the vesicle secretion of the Golgi apparatus, endocytosed and accumulated in the endosome, then transferred to lysosomes where proteolytic cleavage yields three products: a linker peptide, an 8 kDa proheparanase fragment and a 50 kDa proheparanase fragment. The 8kDa and 50kDa fragments form a heterodimer, which constitutes the active HPSE molecule.

Figure 1: A schematic model of heparanase trafficking and function in autophagy (Ralph D. S. 2017)

HPSE activity is highly implicated in cellular invasion and tumor metastasis. HPSE expression is induced in many types of cancer, and increased HPSE level is often associated with increased tumor metastasis and reduced postoperative patient survival. HPSE also exhibits a non-enzymatic function that affects cell signaling, adhesion and migration, and gene expression, adhesion and migration, and gene expression. Interaction of HPSE with cell surface receptors on endothelial cells activates intracellular AKT, PI3K and p38 kinase signaling stimulates cell migration and Src kinase-mediated upregulation of angiogenesis by vascular endothelial growth factor (VEGF).

Initially, HPSE has been identified as an enzyme with glycosidase activity involved in tumor cell invasion. However, over the years, HPSE has been shown to be involved in many other pathological conditions. This enzyme has been shown to be increasingly used as a pharmacological target. HPSE inhibitors are currently being tested in several clinical trials, and some have shown some anti-tumor efficacy.

HPSE Gene Editing Service

CRISPR/Cas9 PlatformCB, a global leading biotechnological company specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products for academic research, biotech research and pharmaceutical drug discovery with excellent quality management and quality assurance capacity. Based on our platform, we can help you effectively control target genes deleted, inserted or point mutated in cells or animals via CRISPR/Cas9 technology.

  • HPSE Gene Editing Cell Line Generation

We have successfully implemented HPSE CRISPR/Cas9 gene edited in both easy-to-transfect cell lines and hard-to-transfect cells. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we will offer you full-length custom HPSE gene editing service from strategy design to final stable cells. Our HPSE gene editing cell line generation services include:

➢ gRNA design and synthesis
➢ Transfect the cell lines you're interested
➢ Select the high expression cells and sort monoclonal cell
➢ Validate the knockout/knockin/point mutation of HPSE by PCR and sequencing
➢ Produce cryogenic preserved vials of stable cells and a final report

Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements.

Other host cell lines available: Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.

  • HPSE Gene Editing Animal Model Generation

CRISPR/Cas9 PlatformCB also has extensive experience in incorporating CRISPR system into animal models, which have been fully recognized by our clients. Tell us your projects' needs, we provide a one-stop-shop HPSE CRISPR/Cas9 gene editing animal service and guarantee at least 2 founders or 3 F1 animals with shorter turnaround time and lower price. Our HPSE gene editing animal model generation services include:

➢ HPSE gene conventional knockout animals
➢ HPSE gene conditional knockout animals
➢ HPSE point mutation animals
➢ HPSE knockin animals

Alternative species: mouse, rat, rabbit, zebrafish, C. elegans, etc.

CRISPR/Cas9 PlatformCB is devoted to providing the best gene editing services and products to a wide range of genomics researchers. To accelerate the achievement of your research goals, our gene editing expert team provides you with custom CRISPR/Cas9 services for any specific gene to help you solve problems encountered during your research. There is no doubt that CRISPR/Cas9 PlatformCB will be your best partner to support your research.

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References

  1. Vlodavsky I. et al. Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis. Nature Medicine. 1999; 5 (7):793-802.
  2. Hulett MD. et al. Cloning of mammalian heparanase, an important enzyme in tumor invasion and metastasis. Nature Medicine.1999; 5 (7): 803-9.
  3. Neta Ilan. et al. Function from within: Autophagy induction by HPSE/heparanase—new possibilities for intervention. Autophagy. 2015; 11(12):2387-2389.
  4. Valentina Masola. et al. Heparanase: A Multitasking Protein Involved in Extracellular Matrix (ECM) Remodeling and Intracellular Events. Cells. 2018; 7(12):236.
  5. Charmaine J. Simeonovic. et al. Heparanase and Autoimmune Diabetes. Front Immunol. 2013; 4: 471.
  6. Ralph D. Sanderson. et al. Heparanase regulation of cancer, autophagy and inflammation: New mechanisms and targets for therapy. FEBS J. 2017; 284(1):42-55.
For research use only. Not intended for any clinical use.

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