Glypican 3: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''Glypican-3''' is a [[protein]] that in humans is encoded by the ''GPC3'' [[gene]].<ref name="pmid8589713">{{cite journal | vauthors = Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D | title = Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome | journal = Nature Genetics | volume = 12 | issue = 3 | pages = 241–7 | date = March 1996 | pmid = 8589713 | pmc =  | doi = 10.1038/ng0396-241 }}</ref><ref name="pmid9787072">{{cite journal | vauthors = Veugelers M, Vermeesch J, Watanabe K, Yamaguchi Y, Marynen P, David G | title = GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome | journal = Genomics | volume = 53 | issue = 1 | pages = 1–11 | date = October 1998 | pmid = 9787072 | pmc =  | doi = 10.1006/geno.1998.5465 }}</ref><ref name="entrez_2719">{{cite web | title = Entrez Gene: GPC3 glypican 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2719| access-date = }}</ref><ref name="pmid17258707">{{cite journal | vauthors = Jakubovic BD, Jothy S | title = Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma | journal = Experimental and Molecular Pathology | volume = 82 | issue = 2 | pages = 184–9 | date = April 2007 | pmid = 17258707 | doi = 10.1016/j.yexmp.2006.10.010 }}</ref> The ''GPC3'' gene is located on human X chromosome (Xq26) where the most common gene (Isoform 2, GenBank Accession No.: NP_004475) encodes a 70-kDa core protein with 580 amino acids.<ref name = "Ho_2011">{{cite journal | vauthors = Ho M, Kim H | title = Glypican-3: a new target for cancer immunotherapy | journal = European Journal of Cancer | volume = 47 | issue = 3 | pages = 333–8 | date = February 2011 | pmid = 21112773 | pmc = 3031711 | doi = 10.1016/j.ejca.2010.10.024 }}</ref> Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).<ref name = "Ho_2011" />  
'''Glypican-3''' is a [[protein]] that in humans is encoded by the ''GPC3'' [[gene]].<ref name="pmid8589713">{{cite journal | vauthors = Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D | title = Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome | journal = Nature Genetics | volume = 12 | issue = 3 | pages = 241–7 | date = March 1996 | pmid = 8589713 | pmc =  | doi = 10.1038/ng0396-241 }}</ref><ref name="pmid9787072">{{cite journal | vauthors = Veugelers M, Vermeesch J, Watanabe K, Yamaguchi Y, Marynen P, David G | title = GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome | journal = Genomics | volume = 53 | issue = 1 | pages = 1–11 | date = October 1998 | pmid = 9787072 | pmc =  | doi = 10.1006/geno.1998.5465 }}</ref><ref name="entrez_2719">{{cite web | title = Entrez Gene: GPC3 glypican 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2719| access-date = }}</ref><ref name="pmid17258707">{{cite journal | vauthors = Jakubovic BD, Jothy S | title = Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma | journal = Experimental and Molecular Pathology | volume = 82 | issue = 2 | pages = 184–9 | date = April 2007 | pmid = 17258707 | doi = 10.1016/j.yexmp.2006.10.010 }}</ref> The ''GPC3'' gene is located on human X chromosome (Xq26) where the most common gene (Isoform 2, GenBank Accession No.: NP_004475) encodes a 70-kDa core protein with 580 amino acids.<ref name = "Ho_2011">{{cite journal | vauthors = Ho M, Kim H | title = Glypican-3: a new target for cancer immunotherapy | journal = European Journal of Cancer | volume = 47 | issue = 3 | pages = 333–8 | date = February 2011 | pmid = 21112773 | pmc = 3031711 | doi = 10.1016/j.ejca.2010.10.024 }}</ref> Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).<ref name = "Ho_2011" />


==Structure and function==
==Structure and function==
The protein core of GPC3 consists of two subunits, where the N-terminal subunit has a size of ~40 kDa and the C-terminal subunit is ~30 kDa.<ref name = "Ho_2011" /> Six glypicans (GPC1-6) have been identified in mammals. Cell surface [[heparan sulfate]] [[proteoglycan]]s are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a [[glycosyl]] [[phosphatidylinositol]] linkage. These proteins may play a role in the control of [[cell division]] and growth regulation.<ref name="entrez_2719"/> GPC3 interacts with both Wnt and frizzled (FZD) to form a complex and triggers downstream signaling.<ref>{{cite journal | vauthors = Li N, Gao W, Zhang YF, Ho M | title = Glypicans as Cancer Therapeutic Targets | journal = Trends in Cancer | volume = 4 | issue = 11 | pages = 741–754 | date = November 2018 | pmid = 30352677 | pmc = 6209326 | doi = 10.1016/j.trecan.2018.09.004 }}</ref>  A biochemical study has revealed that Wnt recognizes a heparan sulfate structure on GPC3 containing IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S significantly enhances the binding of Wnt to the glypican.<ref>{{cite journal | vauthors = Gao W, Xu Y, Liu J, Ho M | title = Epitope mapping by a Wnt-blocking antibody: evidence of the Wnt binding domain in heparan sulfate | journal = Scientific Reports | volume = 6 | pages = 26245 | date = May 2016 | pmid = 27185050 | pmc = 4869111 | doi = 10.1038/srep26245 }}</ref>
The protein core of GPC3 consists of two subunits, where the N-terminal subunit has a size of ~40 kDa and the C-terminal subunit is ~30 kDa.<ref name = "Ho_2011" /> Six glypicans (GPC1-6) have been identified in mammals. Cell surface [[heparan sulfate]] [[proteoglycan]]s are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a [[glycosyl]] [[phosphatidylinositol]] linkage. These proteins may play a role in the control of [[cell division]] and growth regulation.<ref name="entrez_2719"/> GPC3 interacts with both Wnt and frizzled (FZD) to form a complex and triggers downstream signaling.<ref name="Gao W 2018">{{cite journal | vauthors = Li N, Gao W, Zhang YF, Ho M | title = Glypicans as Cancer Therapeutic Targets | journal = Trends in Cancer | volume = 4 | issue = 11 | pages = 741–754 | date = November 2018 | pmid = 30352677 | pmc = 6209326 | doi = 10.1016/j.trecan.2018.09.004 }}</ref>  A biochemical study has revealed that Wnt recognizes a heparan sulfate structure on GPC3 containing IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S significantly enhances the binding of Wnt to the glypican.<ref>{{cite journal | vauthors = Gao W, Xu Y, Liu J, Ho M | title = Epitope mapping by a Wnt-blocking antibody: evidence of the Wnt binding domain in heparan sulfate | journal = Scientific Reports | volume = 6 | pages = 26245 | date = May 2016 | pmid = 27185050 | pmc = 4869111 | doi = 10.1038/srep26245 }}</ref>


==Disease linkage==
==Disease linkage==
Line 9: Line 9:


==Diagnostic utility==
==Diagnostic utility==
Glypican 3 [[immunostaining]] has utility for differentiating [[hepatocellular carcinoma]] (HCC) and dysplastic changes in [[cirrhosis|cirrhotic]] [[liver]]s; HCC stains with glypican 3, while liver with dysplastic changes and/or [[cirrhosis|cirrhotic changes]] does not.<ref>{{cite journal | vauthors = Anatelli F, Chuang ST, Yang XJ, Wang HL | title = Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy | journal = American Journal of Clinical Pathology | volume = 130 | issue = 2 | pages = 219–23 | date = August 2008 | pmid = 18628090 | doi = 10.1309/WMB5PX57Y4P8QCTY }}</ref>  Using the YP7 monoclonal antibody, GPC3 protein expression is found in HCC, not in cholangiocarcinoma.<ref name = "Phung_2012">{{cite journal | vauthors = Phung Y, Gao W, Man YG, Nagata S, Ho M | title = High-affinity monoclonal antibodies to cell surface tumor antigen glypican-3 generated through a combination of peptide immunization and flow cytometry screening | journal = mAbs | volume = 4 | issue = 5 | pages = 592–9 | date = September 2012 | pmid = 22820551 | pmc = 3499300 | doi = 10.4161/mabs.20933 }}</ref> GPC3 is also expressed to a lesser degree in melanoma, ovarian clear-cell carcinomas, yolk sac tumors, neuroblastoma, hepatoblastoma, Wilms' tumor cells, and other tumors.<ref name = "Ho_2011" /> However, the significance of GPC3 as a diagnostic tool for human tumors other than HCC is unclear.
Glypican 3 [[immunostaining]] has utility for differentiating [[hepatocellular carcinoma]] (HCC) and dysplastic changes in [[cirrhosis|cirrhotic]] [[liver]]s; HCC stains with glypican 3, while liver with dysplastic changes and/or [[cirrhosis|cirrhotic changes]] does not.<ref>{{cite journal | vauthors = Anatelli F, Chuang ST, Yang XJ, Wang HL | title = Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy | journal = American Journal of Clinical Pathology | volume = 130 | issue = 2 | pages = 219–23 | date = August 2008 | pmid = 18628090 | doi = 10.1309/WMB5PX57Y4P8QCTY }}</ref>  Using the YP7 murine monoclonal antibody, GPC3 protein expression is found in HCC, not in cholangiocarcinoma.<ref name = "Phung_2012">{{cite journal | vauthors = Phung Y, Gao W, Man YG, Nagata S, Ho M | title = High-affinity monoclonal antibodies to cell surface tumor antigen glypican-3 generated through a combination of peptide immunization and flow cytometry screening | journal = mAbs | volume = 4 | issue = 5 | pages = 592–9 | date = September 2012 | pmid = 22820551 | pmc = 3499300 | doi = 10.4161/mabs.20933 }}</ref> The YP7 murine antibody has been humanized and named as 'hYP7'. <ref>{{Cite journal|last=Zhang|first=Yi-Fan|last2=Ho|first2=Mitchell|date=2016-09-26|title=Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma|url=https://www.ncbi.nlm.nih.gov/pubmed/27667400|journal=Scientific Reports|volume=6|pages=33878|doi=10.1038/srep33878|issn=2045-2322|pmc=PMC5036187|pmid=27667400}}</ref> GPC3 is also expressed to a lesser degree in melanoma, ovarian clear-cell carcinomas, yolk sac tumors, neuroblastoma, hepatoblastoma, Wilms' tumor cells, and other tumors.<ref name = "Ho_2011" /> However, the significance of GPC3 as a diagnostic tool for human tumors other than HCC is unclear.


== Therapeutic potential ==
== Therapeutic potential ==
Glypican 3 is a potential therapeutic target for treating liver cancer and other cancers. <ref>{{cite journal | vauthors = Ho M, Kim H | title = Glypican-3: a new target for cancer immunotherapy | journal = European Journal of Cancer | volume = 47 | issue = 3 | pages = 333–8 | date = February 2011 | pmid = 21112773 | pmc = 3031711 | doi = 10.1016/j.ejca.2010.10.024 }}</ref> <ref>{{cite journal | vauthors = Li N, Gao W, Zhang YF, Ho M | title = Glypicans as Cancer Therapeutic Targets | journal = Trends in Cancer | volume = 4 | issue = 11 | pages = 741–754 | date = November 2018 | pmid = 30352677 | pmc = 6209326 | doi = 10.1016/j.trecan.2018.09.004 }}</ref>. Several therapeutic anti-GPC3 antibodies have been developed. Humanized monoclonal antibodies (GC33<ref>{{cite journal | vauthors = Ishiguro T, Sugimoto M, Kinoshita Y, Miyazaki Y, Nakano K, Tsunoda H, Sugo I, Ohizumi I, Aburatani H, Hamakubo T, Kodama T, Tsuchiya M, Yamada-Okabe H | title = Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer | journal = Cancer Research | volume = 68 | issue = 23 | pages = 9832–8 | date = December 2008 | pmid = 19047163 | doi = 10.1158/0008-5472.CAN-08-1973 }}</ref> , hYP7<ref name = "Phung_2012" /> ) recognize the C-lobe of GPC3. The laboratory of Dr. Mitchell Ho at the National Cancer Institute reported the human single-domain antibody HN3<ref>{{cite journal | vauthors = Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS, Ho M | title = Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 12 | pages = E1083-91 | date = March 2013 | pmid = 23471984 | pmc = 3607002 | doi = 10.1073/pnas.1217868110 }}</ref> targeting the N-lobe of GPC3 and the human monoclonal antibody HS20<ref>{{cite journal | vauthors = Gao W, Kim H, Feng M, Phung Y, Xavier CP, Rubin JS, Ho M | title = Inactivation of Wnt signaling by a human antibody that recognizes the heparan sulfate chains of glypican-3 for liver cancer therapy | journal = Hepatology | volume = 60 | issue = 2 | pages = 576–87 | date = August 2014 | pmid = 24492943 | pmc = 4083010 | doi = 10.1002/hep.26996 }}</ref><ref>{{cite journal | vauthors = Kim H, Ho M | title = Isolation of Antibodies to Heparan Sulfate on Glypicans by Phage Display | journal = Current Protocols in Protein Science | volume = 94 | issue = 1 | pages = e66 | date = November 2018 | pmid = 30091851 | pmc = 6205898 | doi = 10.1002/cpps.66 }}</ref> targeting the heparan sulfate chains of GPC3 by phage display technology. Both HN3 and HS20 antibodies inhibit Wnt signaling in liver cancer cells . The immunotoxins based on HN3 <ref>{{cite journal | vauthors = Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, Ho M | title = Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis | journal = Nature Communications | volume = 6 | pages = 6536 | date = March 2015 | pmid = 25758784 | pmc = 4357278 | doi = 10.1038/ncomms7536 }}</ref><ref>{{cite journal | vauthors = Wang C, Gao W, Feng M, Pastan I, Ho M | title = Construction of an immunotoxin, HN3-mPE24, targeting glypican-3 for liver cancer therapy | journal = Oncotarget | volume = 8 | issue = 20 | pages = 32450–32460 | date = May 2017 | pmid = 27419635 | pmc = 5464801 | doi = 10.18632/oncotarget.10592 }}</ref> and antibody-drug conjugates based on hYP7 <ref>{{cite journal | vauthors = Fu Y, Urban DJ, Nani RR, Zhang YF, Li N, Fu H, Shah H, Gorka AP, Guha R, Chen L, Hall MD, Schnermann MJ, Ho M | title = Glypican-3 Specific Antibody Drug Conjugates Targeting Hepatocellular Carcinoma | journal = Hepatology | date = October 2018 | pmid = 30353932 | doi = 10.1002/hep.30326 }}</ref> have been developed for treating liver cancer.  
Glypican 3 is a potential therapeutic target for treating liver cancer and other cancers.<ref name="Ho_2011"/><ref name="Gao W 2018"/> Several therapeutic anti-GPC3 antibodies have been developed. Humanized monoclonal antibodies (GC33,<ref>{{cite journal | vauthors = Ishiguro T, Sugimoto M, Kinoshita Y, Miyazaki Y, Nakano K, Tsunoda H, Sugo I, Ohizumi I, Aburatani H, Hamakubo T, Kodama T, Tsuchiya M, Yamada-Okabe H | title = Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer | journal = Cancer Research | volume = 68 | issue = 23 | pages = 9832–8 | date = December 2008 | pmid = 19047163 | doi = 10.1158/0008-5472.CAN-08-1973 }}</ref> hYP7<ref name = "Phung_2012" /> ) recognize the C-lobe of GPC3. The laboratory of Dr. Mitchell Ho at the National Cancer Institute reported the human single-domain antibody HN3<ref>{{cite journal | vauthors = Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS, Ho M | title = Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 12 | pages = E1083-91 | date = March 2013 | pmid = 23471984 | pmc = 3607002 | doi = 10.1073/pnas.1217868110 }}</ref> targeting the N-lobe of GPC3 and the human monoclonal antibody HS20<ref>{{cite journal | vauthors = Gao W, Kim H, Feng M, Phung Y, Xavier CP, Rubin JS, Ho M | title = Inactivation of Wnt signaling by a human antibody that recognizes the heparan sulfate chains of glypican-3 for liver cancer therapy | journal = Hepatology | volume = 60 | issue = 2 | pages = 576–87 | date = August 2014 | pmid = 24492943 | pmc = 4083010 | doi = 10.1002/hep.26996 }}</ref><ref>{{cite journal | vauthors = Kim H, Ho M | title = Isolation of Antibodies to Heparan Sulfate on Glypicans by Phage Display | journal = Current Protocols in Protein Science | volume = 94 | issue = 1 | pages = e66 | date = November 2018 | pmid = 30091851 | pmc = 6205898 | doi = 10.1002/cpps.66 }}</ref> targeting the heparan sulfate chains of GPC3 by phage display technology. Both HN3 and HS20 antibodies inhibit Wnt signaling in liver cancer cells . The immunotoxins based on HN3 <ref>{{cite journal | vauthors = Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, Ho M | title = Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis | journal = Nature Communications | volume = 6 | pages = 6536 | date = March 2015 | pmid = 25758784 | pmc = 4357278 | doi = 10.1038/ncomms7536 }}</ref><ref>{{cite journal | vauthors = Wang C, Gao W, Feng M, Pastan I, Ho M | title = Construction of an immunotoxin, HN3-mPE24, targeting glypican-3 for liver cancer therapy | journal = Oncotarget | volume = 8 | issue = 20 | pages = 32450–32460 | date = May 2017 | pmid = 27419635 | pmc = 5464801 | doi = 10.18632/oncotarget.10592 }}</ref> and antibody-drug conjugates based on hYP7 <ref>{{cite journal | vauthors = Fu Y, Urban DJ, Nani RR, Zhang YF, Li N, Fu H, Shah H, Gorka AP, Guha R, Chen L, Hall MD, Schnermann MJ, Ho M | title = Glypican-3 Specific Antibody Drug Conjugates Targeting Hepatocellular Carcinoma | journal = Hepatology | date = October 2018 | pmid = 30353932 | doi = 10.1002/hep.30326 }}</ref> have been developed for treating liver cancer.


== See also ==
== See also ==
* [[Glypican]]
* [[Glypican]]
{{clear}}
{{clear}}
== References ==
== References ==
{{reflist}}
{{reflist}}
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[[Category:Immunologic tests]]
[[Category:Immunologic tests]]
{{gene-X-stub}}

Latest revision as of 16:28, 18 January 2019

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Glypican-3 is a protein that in humans is encoded by the GPC3 gene.[1][2][3][4] The GPC3 gene is located on human X chromosome (Xq26) where the most common gene (Isoform 2, GenBank Accession No.: NP_004475) encodes a 70-kDa core protein with 580 amino acids.[5] Three variants have been detected that encode alternatively spliced forms termed Isoforms 1 (NP_001158089), Isoform 3 (NP_001158090) and Isoform 4 (NP_001158091).[5]

Structure and function

The protein core of GPC3 consists of two subunits, where the N-terminal subunit has a size of ~40 kDa and the C-terminal subunit is ~30 kDa.[5] Six glypicans (GPC1-6) have been identified in mammals. Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation.[3] GPC3 interacts with both Wnt and frizzled (FZD) to form a complex and triggers downstream signaling.[6] A biochemical study has revealed that Wnt recognizes a heparan sulfate structure on GPC3 containing IdoA2S and GlcNS6S, and that the 3-O-sulfation in GlcNS6S3S significantly enhances the binding of Wnt to the glypican.[7]

Disease linkage

Deletion mutations in this gene are associated with Simpson-Golabi-Behmel syndrome.[8]

Diagnostic utility

Glypican 3 immunostaining has utility for differentiating hepatocellular carcinoma (HCC) and dysplastic changes in cirrhotic livers; HCC stains with glypican 3, while liver with dysplastic changes and/or cirrhotic changes does not.[9] Using the YP7 murine monoclonal antibody, GPC3 protein expression is found in HCC, not in cholangiocarcinoma.[10] The YP7 murine antibody has been humanized and named as 'hYP7'. [11] GPC3 is also expressed to a lesser degree in melanoma, ovarian clear-cell carcinomas, yolk sac tumors, neuroblastoma, hepatoblastoma, Wilms' tumor cells, and other tumors.[5] However, the significance of GPC3 as a diagnostic tool for human tumors other than HCC is unclear.

Therapeutic potential

Glypican 3 is a potential therapeutic target for treating liver cancer and other cancers.[5][6] Several therapeutic anti-GPC3 antibodies have been developed. Humanized monoclonal antibodies (GC33,[12] hYP7[10] ) recognize the C-lobe of GPC3. The laboratory of Dr. Mitchell Ho at the National Cancer Institute reported the human single-domain antibody HN3[13] targeting the N-lobe of GPC3 and the human monoclonal antibody HS20[14][15] targeting the heparan sulfate chains of GPC3 by phage display technology. Both HN3 and HS20 antibodies inhibit Wnt signaling in liver cancer cells . The immunotoxins based on HN3 [16][17] and antibody-drug conjugates based on hYP7 [18] have been developed for treating liver cancer.

See also

References

  1. ↑ Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D (March 1996). "Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome". Nature Genetics. 12 (3): 241–7. doi:10.1038/ng0396-241. PMID 8589713.
  2. ↑ Veugelers M, Vermeesch J, Watanabe K, Yamaguchi Y, Marynen P, David G (October 1998). "GPC4, the gene for human K-glypican, flanks GPC3 on xq26: deletion of the GPC3-GPC4 gene cluster in one family with Simpson-Golabi-Behmel syndrome". Genomics. 53 (1): 1–11. doi:10.1006/geno.1998.5465. PMID 9787072.
  3. ↑ 3.0 3.1 "Entrez Gene: GPC3 glypican 3".
  4. ↑ Jakubovic BD, Jothy S (April 2007). "Glypican-3: from the mutations of Simpson-Golabi-Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma". Experimental and Molecular Pathology. 82 (2): 184–9. doi:10.1016/j.yexmp.2006.10.010. PMID 17258707.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Ho M, Kim H (February 2011). "Glypican-3: a new target for cancer immunotherapy". European Journal of Cancer. 47 (3): 333–8. doi:10.1016/j.ejca.2010.10.024. PMC 3031711. PMID 21112773.
  6. ↑ 6.0 6.1 Li N, Gao W, Zhang YF, Ho M (November 2018). "Glypicans as Cancer Therapeutic Targets". Trends in Cancer. 4 (11): 741–754. doi:10.1016/j.trecan.2018.09.004. PMC 6209326. PMID 30352677.
  7. ↑ Gao W, Xu Y, Liu J, Ho M (May 2016). "Epitope mapping by a Wnt-blocking antibody: evidence of the Wnt binding domain in heparan sulfate". Scientific Reports. 6: 26245. doi:10.1038/srep26245. PMC 4869111. PMID 27185050.
  8. ↑ Davoodi J, Kelly J, Gendron NH, MacKenzie AE (June 2007). "The Simpson-Golabi-Behmel syndrome causative glypican-3, binds to and inhibits the dipeptidyl peptidase activity of CD26". Proteomics. 7 (13): 2300–10. doi:10.1002/pmic.200600654. PMID 17549790.
  9. ↑ Anatelli F, Chuang ST, Yang XJ, Wang HL (August 2008). "Value of glypican 3 immunostaining in the diagnosis of hepatocellular carcinoma on needle biopsy". American Journal of Clinical Pathology. 130 (2): 219–23. doi:10.1309/WMB5PX57Y4P8QCTY. PMID 18628090.
  10. ↑ 10.0 10.1 Phung Y, Gao W, Man YG, Nagata S, Ho M (September 2012). "High-affinity monoclonal antibodies to cell surface tumor antigen glypican-3 generated through a combination of peptide immunization and flow cytometry screening". mAbs. 4 (5): 592–9. doi:10.4161/mabs.20933. PMC 3499300. PMID 22820551.
  11. ↑ Zhang, Yi-Fan; Ho, Mitchell (2016-09-26). "Humanization of high-affinity antibodies targeting glypican-3 in hepatocellular carcinoma". Scientific Reports. 6: 33878. doi:10.1038/srep33878. ISSN 2045-2322. PMC 5036187. PMID 27667400.
  12. ↑ Ishiguro T, Sugimoto M, Kinoshita Y, Miyazaki Y, Nakano K, Tsunoda H, Sugo I, Ohizumi I, Aburatani H, Hamakubo T, Kodama T, Tsuchiya M, Yamada-Okabe H (December 2008). "Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer". Cancer Research. 68 (23): 9832–8. doi:10.1158/0008-5472.CAN-08-1973. PMID 19047163.
  13. ↑ Feng M, Gao W, Wang R, Chen W, Man YG, Figg WD, Wang XW, Dimitrov DS, Ho M (March 2013). "Therapeutically targeting glypican-3 via a conformation-specific single-domain antibody in hepatocellular carcinoma". Proceedings of the National Academy of Sciences of the United States of America. 110 (12): E1083–91. doi:10.1073/pnas.1217868110. PMC 3607002. PMID 23471984.
  14. ↑ Gao W, Kim H, Feng M, Phung Y, Xavier CP, Rubin JS, Ho M (August 2014). "Inactivation of Wnt signaling by a human antibody that recognizes the heparan sulfate chains of glypican-3 for liver cancer therapy". Hepatology. 60 (2): 576–87. doi:10.1002/hep.26996. PMC 4083010. PMID 24492943.
  15. ↑ Kim H, Ho M (November 2018). "Isolation of Antibodies to Heparan Sulfate on Glypicans by Phage Display". Current Protocols in Protein Science. 94 (1): e66. doi:10.1002/cpps.66. PMC 6205898. PMID 30091851.
  16. ↑ Gao W, Tang Z, Zhang YF, Feng M, Qian M, Dimitrov DS, Ho M (March 2015). "Immunotoxin targeting glypican-3 regresses liver cancer via dual inhibition of Wnt signalling and protein synthesis". Nature Communications. 6: 6536. doi:10.1038/ncomms7536. PMC 4357278. PMID 25758784.
  17. ↑ Wang C, Gao W, Feng M, Pastan I, Ho M (May 2017). "Construction of an immunotoxin, HN3-mPE24, targeting glypican-3 for liver cancer therapy". Oncotarget. 8 (20): 32450–32460. doi:10.18632/oncotarget.10592. PMC 5464801. PMID 27419635.
  18. ↑ Fu Y, Urban DJ, Nani RR, Zhang YF, Li N, Fu H, Shah H, Gorka AP, Guha R, Chen L, Hall MD, Schnermann MJ, Ho M (October 2018). "Glypican-3 Specific Antibody Drug Conjugates Targeting Hepatocellular Carcinoma". Hepatology. doi:10.1002/hep.30326. PMID 30353932.

Further reading

External links

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