Glypican 2
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
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
Summarize
Perspective
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
References
External links
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