You are here: Home Page > Information > Apoptosis > Netrin-1 – Neuron Guidance Factor Involved in iPS Regulation and Tumourigenesis

Netrin-1 – Neuron Guidance Factor Involved in iPS Regulation and Tumourigenesis

Netrin-1 – Neuron Guidance Factor Involved in iPS Regulation and Tumourigenesis

Netrin-1 is a member of the laminin-like protein family and was initially identified as a potent chemotactic molecule involved in axonal guidance and cell migration during embryonic development. It is a neuronal guidance protein (NGP) that triggers either attraction or repulsion effects on migrating axons of neurons, interacting with the receptors DCC or UNC5 (A-D).

Netrin-1 serves as a survival factor via its association with its receptors which prevent the initiation of apoptosis and is involved in tumourigenesis. Netrin-1 regulates inflammation and leukocyte infiltration, suggesting roles for netrin-1 in the immune response. Netrin-1 regulates endothelial cell adhesion and angiogenesis, macrophage migration and apoptosis, smooth muscle cells (SMCs) phenotypic dedifferentiation and mobility, chemokine activities, and inflammatory responses during atherosclerosis initiation and progression.

Netrin-1 protects neurons from death during development and favours tumour epithelial cell survival in some types of cancers. It interacts with the orphan amyloid precursor protein (APP), a protein component of the amyloid plaques that are associated with Alzheimer’s disease (AD). Netrin-1 also inhibits the remyelination of neurons in Multiple Sclerosis (MS) (and other progressive demyelinating diseases) by inhibiting oligodendrocyte precursor migration. Netrin-1 has been described to be the 5th Element of classical iPS cell factors. Netrin-1’s function in protecting embryonic stem cells from apoptosis and the addition of recombinant Netrin-1 improves the generation of mouse and human iPS cells (induced Pluripotent Stem Cells).

Members of the UNC5 receptor family (UNC5A-D) have been identified as dependence receptors whose functions depend on the availability of their ligand netrin-1. Through binding to netrin-1, these receptors transmit signals for cell survival, migration and differentiation, and participate in diverse physiological and pathological processes. In the lack of netrin-1, however, these receptors initiate apoptosis-inducing signals. Netrin-1 is therefore a prosurvival factor acting by blocking cell death induced by its unbound receptors.

Netrin-1 and its receptors play a role in tumourigenesis and tumour progression. The expression of the UNC5 receptor family is down-regulated in a variety of human tumours and Netrin-1 is overexpressed in a large number of aggressive cancers. Expression aberrance of the UNC5 receptor family in tumours is caused by diverse mechanisms including genomic, epigenetic, transcriptional and post-transcriptional regulation. Blocking netrin-1 binding to its receptors induces apoptotic cell death in tumour cells. A recently developed novel therapy based on functional blocking antibodies aims at inhibiting the binding of Netrin-1 to these receptors to trigger cell death by apoptosis.

Figure: Netrin-1 and the dependence receptor signalling pathways. Adapted from: Netrin-1 and its receptors in tumorigenesis: H. Arakawa; Nat. Rev. Cancer 4, 978 (2004)

Literature References:

  1. Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance: D. Ozmadenci, et al.; Nat. Commun. 6, 7398 (2015)
  2. Revisiting Netrin-1: One Who Guides (Axons): N.P. Boyer & S.L. Gupton; Front. Cell Neurosci. 12, 221 (2018)
  3. Netrin-1 in Glioblastoma Neovascularization: The New Partner in Crime? X. Vasquez, et al.; Int. J. Mol. Sci. 22, 8248 (2021)
  4. UNC5 dependence receptor family in human cancer: A controllable double-edged sword: Y. Zhu, et al.; Cancer Lett. 516, 28 (2021)
  5. Netrin-1: A Modulator of Macrophage Driven Acute and Chronic Inflammation: L. Ziegon & M. Schlegel; Int. J. Mol. Sci. 23, 275 (2021)
  6. Netrin-1: An emerging player in inflammatory diseases: X. Xia, et al.; Cytokine Growth Factor Rev. 64, 46 (2022)

Potent Functional Antibody for Blocking Netrin-1 Signaling Pathways In Vivo

anti-Netrin-1 (human), mAb (rec.) (blocking) (2F5) (preservative-free) 

AG-27B-0018PF (100 µg, 500 µg sizes & Bulk from Stock)

AdipoGen Life Sciences is the developer and manufacturer of the recombinant antibody clone 2F5, a potent antibody that inhibits the activation of human and mouse Netrin-1 to human or mouse receptors DCC or UNC5 (KD antibody-Netrin-1 is 1.5nM) for in vivo blocking application. This antibody has been used successfully in scientific publications on neurodegeneration, tumourigenesis, angiogenesis and arthritis research.

This antibody is available as a preservative-free version and in BULK quantities for long-term studies.

Product Specifications:

Clone:                2F5
Isotype:              Human IgG2λ
Immunogen:      Recombinant human Netrin-1
Applications:     Functional (Blocking), ELISA
Crossreactivity: Human, Mouse
Purity:                <95% (SDS-PAGE), Protein-A affinity purified.

Figure: anti-Netrin-1 (human), mAb (rec.) (blocking) (2F5) (preservative free) (Prod. No. AG-27B-0018PF) blocks tumour growth in vivo. Method: Tumour cells (OCI-Ly3) were implanted in SCID mice by subcutaneous injection of 3×106 cells in 100µl of PBS. When tumours reached 150mm3, mice received intraperitoneal injections of blocking anti-Netrin-1 mAb (2F5) at 20 mg/kg or an equal volume of the antibody control anti-Netrin-1 (human), mAb (rec.) (H4) (preservative free) (Prod. No. AG-27B-0020PF) every two days. Tumor growth rates from the beginning of treatment are shown.

Selected Product References:

  1. Epidermal Growth Factor Receptor-Dependent Mutual Amplification between Netrin-1 and the Hepatitis C Virus: M.L. Plissonnier, et al.; PLoS Biol. 14, e1002421 (2016)
  2. Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas: T. Broutier, et al.; EMBO Mol. Med. 8, 96 (2016)
  3. Netrin-1 acts as a non-canonical angiogenic factor produced by human Wharton’s jelly mesenchymal stem cells (WJ-MSC): C.P. Prieto, et al.; Stem Cell Res. Ther. 8, 43 (2017)
  4. Downregulation of the Netrin-1 Receptor UNC5b Underlies Increased Placental Angiogenesis in Human Gestational Diabetes Mellitus: C.P. Prieto, et al.; Int. J. Mol. Sci. 20, 1408 (2019)
  5. Netrin-1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson’s disease features: M. Jasmin, et al.; EMBO J. 40, e105537 (2021)
  6. Netrin-1 Secreted by Human Osteoarthritic Articular Chondrocytes Promotes Angiogenesis in Vitro: J. Akoum, et al.; Cartilage 13, 94 (2022)

Biologically Active Netrin-1 for iPS Cells Generation: The 5th Key Reprogramming Factor

Netrin-1 (human): Fc (human) (rec.)

AG-40B-0075 (10 µg, 3 x 10 µg; 100 µg sizes & Bulk from Stock)

Netrin-1 (human) (rec.)

AG-40B-0040 (10 µg, 3 x 10 µg; 100 µg sizes & Bulk from Stock)

AdipoGen Life Sciences is the developer and manufacturer of biologically active human Netrin-1. These proteins have a unique and improved formulation which leads to higher protein stability & activity, no aggregation nor precipitation (as known for several preparations from competitors), and no inclusion of BSA. The proteins cross-react with the human, mouse and rat receptors and have been published in scientific literature.

These recombinant proteins are available in BULK quantities.

Selected Product References:

  1. DCC constrains tumour progression via its dependence receptor activity: M. Castets, et al.; Nature 482, 534 (2011)
  2. Netrin-1 regulates somatic cell reprogramming and pluripotency maintenance: D. Ozmadenci, et al.; Nat. Commun. 6, ID7398 (2015)
  3. Targeting netrin‐1/DCC interaction in diffuse large B‐cell and mantle cell lymphomas: L. Broutier, et al.; EMBO Mol. Med. 8, 96 (2016)
  4. Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers: M. Grandin, et al.; Cancer Cell 29, 173 (2016)
  5. Ultrasound molecular imaging as a non-invasive companion diagnostic for netrin-1 interference therapy in breast cancer: J. Wischhusen, et al.; Theranostics 8, 5126 (2018)

All Netrin-Related Research Products  

Product NameProduct CodeIsotypeApplicationsSpecies
anti-Netrin-1 (human), mAb (rec.) (blocking) (2F5) (preservative-free)AG-27B-0018PFHuman IgG2λFunctional, ELISAHuman, Mouse
anti-Netrin-1 (human), mAb (rec.) (H4) (preservative-free)AG-27B-0020PFHuman IgG2λFunctional (negative control), ELISAHuman, Mouse
anti-Netrin-4, mAb (Nely-1)AG-20B-0039Mouse IgG1κELISA, Western BlotHuman, Mouse
Product NameProduct CodeSourceEndotoxinSpecies
Netrin-1 (human):Fc (human) (rec.)AG-40B-0075HEK 293 cells<0.1EU/μgHuman, Mouse, Rat
Netrin-1 (human) (rec.)AG-40B-0040HEK 293 cells<0.01EU/μgHuman, Mouse, Rat
UNC5B (human):Fc (human) (rec.)AG-40B-0037HEK 293 cells<0.1EU/μgHuman, Mouse

Originally posted by Adipogen on: https://adipogen.com/netrin

Caltag Medsystems is the distributor of Adipogen products in the UK and Ireland. If you have any questions about these products, please contact us.

Netrin-1 – Neuron Guidance Factor Involved in iPS Regulation and Tumourigenesis
Tagged on:             

Contact us