Glypican 2

GPC2
Identifiers
Aliases	GPC2 , Glypican 2
External IDs	OMIM: 618446; MGI: 1919201; HomoloGene: 17657; GeneCards: GPC2; OMA:GPC2 - orthologs
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q22.1 Start 100,169,606 bp [1] End 100,177,381 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 G2 Start 138,271,917 bp [2] End 138,278,267 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence skin of arm ventricular zone sperm tendon of biceps brachii pericardium thymus buccal mucosa cell testicle left testis Top expressed in ganglionic eminence mesencephalon ventricular zone neural tube genital tubercle spermatocyte granulocyte lens epiblast tail of embryo More reference expression data BioGPS n/a
Gene ontology Molecular function heparan sulfate proteoglycan binding protein binding Cellular component membrane plasma membrane extracellular region lysosomal lumen endoplasmic reticulum Golgi lumen anchored component of membrane extracellular space anchored component of plasma membrane collagen-containing extracellular matrix cell surface synapse Biological process retinoid metabolic process glycosaminoglycan catabolic process glycosaminoglycan biosynthetic process neuron differentiation smoothened signaling pathway regulation of signal transduction positive regulation of neuron projection development cell migration regulation of protein localization to membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 221914 71951 Ensembl ENSG00000213420 ENSMUSG00000029510 UniProt Q8N158 Q8BKV1 RefSeq (mRNA) NM_152742 NM_172412 RefSeq (protein) NP_689955 NP_766000 Location (UCSC) Chr 7: 100.17 – 100.18 Mb Chr 5: 138.27 – 138.28 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Glypican 2 (GPC2), also known cerebroglycan, is a protein which in humans is encoded by the GPC2 gene. ^{[5] [6]} The GPC2 gene is at locus 7q22.1 and encodes for a 579 amino acid protein. ^[7] The C-terminus of GPC2 has the GPI attachment site, at G554, and the N-terminus encodes a signal peptide, from M1 to S24. Multiple GPC2 mRNA transcripts have been identified. ^[8] GPC2-201 is the isoform overexpressed in pediatric cancers. Tumor-associated exon 3 of GPC2 shows the lowest expression in normal tissues compared with other exons. ^[8]

Function

Cerebroglycan is a glycophosphatidylinositol-linked integral membrane heparan sulfate proteoglycan found in the developing nervous system. Cerebroglycan participates in cell adhesion and is thought to regulate the growth and guidance of axons. ^[9] Cerebroglycan has especially high affinity for laminin-1. ^[10]

Implications in cancer

GPC2 has been identified as a therapeutic target in neuroblastoma in two independent studies published by Mitchell Ho's lab at the NCI and John Maris's lab at the University of Pennsylvania in 2017. ^{[11] [12]} GPC2 is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival. ^{[11] [13]} GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. ^[11] Chimeric antigen receptor (CAR) T cells and Immunotoxins (antibody-cytotoxin fusion proteins) targeting GPC2 inhibit neuroblastoma growth in mouse models. ^[11] The Ho lab at the National Cancer Institute generated a mouse monoclonal antibody called CT3 targeting human GPC2. ^[8] The CT3 antibody has been shown to recognize a tumor-associated isoform (isoform 201) of GPC2 with high affinity. ^[8] Immunohistochemistry using CT3 shows that the antibody has high binding signals on neuroblastoma, medulloblastoma, and retinoblastoma. ^[8] CT3 does not bind human normal tissues except the testis. ^[8] CT3-derived CAR T cells regress neuroblastoma in mice. ^{[8] [14]} The CT3 mAb is commercially available for Western blot, flow cytometry, immunohistochemistry, and immunofluorescence. A GPC2 specific antibody-drug conjugate (ADC) can inhibit neuroblastoma and small-cell lung cancer cell proliferation and tumor growth in mice. ^{[12] [15]}

See also

• Glypican

References

1. GRCh38: Ensembl release 89: ENSG00000213420 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029510 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Stipp CS, Litwack ED, Lander AD (January 1994). "Cerebroglycan: an integral membrane heparan sulfate proteoglycan that is unique to the developing nervous system and expressed specifically during neuronal differentiation". The Journal of Cell Biology. 124 (1–2): 149–160. doi:10.1083/jcb.124.1.149. PMC   2119891 . PMID   8294498.
6. "Entrez Gene: GPC2 glypican 2".
7. Li N, Spetz MR, Li D, Ho M (July 2021). "Advances in immunotherapeutic targets for childhood cancers: A focus on glypican-2 and B7-H3". Pharmacology & Therapeutics. 223: 107892. doi:10.1016/j.pharmthera.2021.107892. PMC   8202769 . PMID   33992682.
8. Li N, Torres MB, Spetz MR, Wang R, Peng L, Tian M, et al. (June 2021). "CAR T cells targeting tumor-associated exons of glypican 2 regress neuroblastoma in mice". Cell Reports. Medicine. 2 (6): 100297. doi:10.1016/j.xcrm.2021.100297. PMC   8233664 . PMID   34195677.
9. Ivins JK, Litwack ED, Kumbasar A, Stipp CS, Lander AD (April 1997). "Cerebroglycan, a developmentally regulated cell-surface heparan sulfate proteoglycan, is expressed on developing axons and growth cones". Developmental Biology. 184 (2): 320–332. doi: 10.1006/dbio.1997.8532 . PMID   9133438. S2CID   23283933.
10. Herndon ME, Stipp CS, Lander AD (February 1999). "Interactions of neural glycosaminoglycans and proteoglycans with protein ligands: assessment of selectivity, heterogeneity and the participation of core proteins in binding". Glycobiology. 9 (2): 143–155. doi: 10.1093/glycob/9.2.143 . PMID   9949192.
11. Li N, Fu H, Hewitt SM, Dimitrov DS, Ho M (August 2017). "Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma". Proceedings of the National Academy of Sciences of the United States of America. 114 (32): E6623 –E6631. Bibcode:2017PNAS..114E6623L. doi: 10.1073/pnas.1706055114 . PMC   5559039 . PMID   28739923.
12. Bosse KR, Raman P, Zhu Z, Lane M, Martinez D, Heitzeneder S, et al. (September 2017). "Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma". Cancer Cell. 32 (3): 295–309.e12. doi:10.1016/j.ccell.2017.08.003. PMC   5600520 . PMID   28898695.
13. Li N, Spetz MR, Ho M (December 2020). "The Role of Glypicans in Cancer Progression and Therapy". The Journal of Histochemistry and Cytochemistry. 68 (12): 841–862. doi:10.1369/0022155420933709. PMC   7711243 . PMID   32623934.
14. Sun M, Cao Y, Okada R, Reyes-González JM, Stack HG, Qin H, et al. (January 2023). "Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma". Journal for Immunotherapy of Cancer. 11 (1): e005881. doi:10.1136/jitc-2022-005881. PMC   9835961 . PMID   36631162.
15. Raman S, Buongervino SN, Lane MV, Zhelev DV, Zhu Z, Cui H, et al. (July 2021). "A GPC2 antibody-drug conjugate is efficacious against neuroblastoma and small-cell lung cancer via binding a conformational epitope". Cell Reports. Medicine. 2 (7): 100344. doi:10.1016/j.xcrm.2021.100344. PMC   8324494 . PMID   34337560.

External links

• GPC2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)