Glypican 2
Template:Short description Template:Cs1 config Template:Infobox gene Glypican 2 (GPC2), also known cerebroglycan, is a protein which in humans is encoded by the GPC2 gene.[1][2] The GPC2 gene is at locus 7q22.1 and encodes for a 579 amino acid protein.[3] 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.[4] 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.[4]
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.[5] Cerebroglycan has especially high affinity for laminin-1.[6]
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.[7][8] GPC2 is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival.[7][9] GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of N-Myc, an oncogenic driver of neuroblastoma tumorigenesis.[7] Chimeric antigen receptor (CAR) T cells and Immunotoxins (antibody-cytotoxin fusion proteins) targeting GPC2 inhibit neuroblastoma growth in mouse models.[7] The Ho lab at the National Cancer Institute generated a mouse monoclonal antibody called CT3 targeting human GPC2.[4] The CT3 antibody has been shown to recognize a tumor-associated isoform (isoform 201) of GPC2 with high affinity.[4] Immunohistochemistry using CT3 shows that the antibody has high binding signals on neuroblastoma, medulloblastoma, and retinoblastoma.[4] CT3 does not bind human normal tissues except the testis.[4] CT3-derived CAR T cells regress neuroblastoma in mice.[4][10] 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.[8][11]
See also
References
<templatestyles src="Reflist/styles.css" />
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b c d e f g Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ a b c d Script error: No such module "Citation/CS1".
- ↑ a b Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
- ↑ Script error: No such module "Citation/CS1".
Script error: No such module "Check for unknown parameters".