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Gene Review

Gpc3  -  glypican 3

Mus musculus

Synonyms: Glypican-3, OCI-5
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Disease relevance of Gpc3

  • Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model [1].
  • Upon injection into syngeneic BALB/c mice LM3-GPC3 clones showed less local invasiveness and developed fewer spontaneous and experimental lung metastasis than controls [1].
  • The transfer of ES-DC-GPC3 protected the recipient mice from subsequent challenge with B16-F10 melanoma, naturally expressing glypican-3, and with glypican-3-transfectant MCA205 sarcoma [2].

High impact information on Gpc3


Biological context of Gpc3

  • The kidney of the Gpc3-/ mouse, a novel model of human renal dysplasia, is characterized by selective degeneration of medullary collecting ducts preceded by enhanced cell proliferation and overgrowth during branching morphogenesis [5].
  • Mice carrying mutant alleles of Gpc3 created by either targeted gene disruption or gene trapping display a wide range of phenotypes associated with SGBS including renal cystic dysplasia, ventral wall defects, and skeletal abnormalities that are consistent with the pattern of Gpc3 expression in the mouse embryo [6].
  • Reduction of Gpc3 gene dosage also increased UB cell proliferation, an effect that was enhanced in Gpc3+/-;Bmp2+/- mice to an extent greater than the sum of that observed in Gpc3+/- and Bmp2+/- mice [7].
  • These results demonstrate that BMP2-SMAD signaling, modulated by GPC3, inhibits renal branching morphogenesis in vivo [7].
  • GPC3-expressing cells were more sensitive to apoptosis induced by serum depletion, exhibited a delay in the first steps of spreading and were less motile than controls [1].

Anatomical context of Gpc3

  • Mice carrying a Gpc3 gene knockout exhibited several phenotypic features that resemble clinical hallmarks of SGBS1, including somatic overgrowth, renal dysplasia, accessory spleens, polydactyly, and placentomegaly [8].
  • Gpc-3 mRNA appears across the ventral neural tube, then in the lamina terminalis and hypothalamus [9].
  • LM3, a murine mammary tumor cell line unable to express GPC3, was stably transfected with the rat GPC3 gene to analyze its role in tumor progression [1].
  • Glypican-3 (GPC3), a proteoglycan bound to the cell membrane through a GPI anchor, is widely expressed in the embryo but down regulated in most adult tissues, with some exceptions as mammary cells [1].
  • Similar comparative differences were found in collecting duct cell lines derived from GPC3-deficient and wild type mice and induced to form tubular progenitors in vitro, suggesting that GPC3 directly controls collecting duct cell responses [5].

Associations of Gpc3 with chemical compounds

  • Murine models have been used to study the effects of targeted deletions of the genes p57KIP2 and GPC3, as well as overexpression of IGF2 [10].

Other interactions of Gpc3


Analytical, diagnostic and therapeutic context of Gpc3

  • In conclusion, the usefulness of glypican-3 as a target antigen for antimelanoma immunotherapy was thus shown in the mouse model using the ES-DC system [2].


  1. Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model. Peters, M.G., Farías, E., Colombo, L., Filmus, J., Puricelli, L., Bal de Kier Joffé, E. Breast Cancer Res. Treat. (2003) [Pubmed]
  2. Embryonic stem cell-derived dendritic cells expressing glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma, B16-F10. Motomura, Y., Senju, S., Nakatsura, T., Matsuyoshi, H., Hirata, S., Monji, M., Komori, H., Fukuma, D., Baba, H., Nishimura, Y. Cancer Res. (2006) [Pubmed]
  3. Glypican-3 expression is silenced in human breast cancer. Xiang, Y.Y., Ladeda, V., Filmus, J. Oncogene (2001) [Pubmed]
  4. Altered hematopoiesis in glypican-3-deficient mice results in decreased osteoclast differentiation and a delay in endochondral ossification. Viviano, B.L., Silverstein, L., Pflederer, C., Paine-Saunders, S., Mills, K., Saunders, S. Dev. Biol. (2005) [Pubmed]
  5. Glypican-3 modulates BMP- and FGF-mediated effects during renal branching morphogenesis. Grisaru, S., Cano-Gauci, D., Tee, J., Filmus, J., Rosenblum, N.D. Dev. Biol. (2001) [Pubmed]
  6. glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Paine-Saunders, S., Viviano, B.L., Zupicich, J., Skarnes, W.C., Saunders, S. Dev. Biol. (2000) [Pubmed]
  7. Glypican-3 modulates inhibitory Bmp2-Smad signaling to control renal development in vivo. Hartwig, S., Hu, M.C., Cella, C., Piscione, T., Filmus, J., Rosenblum, N.D. Mech. Dev. (2005) [Pubmed]
  8. Overgrowth of a mouse model of the Simpson-Golabi-Behmel syndrome is independent of IGF signaling. Chiao, E., Fisher, P., Crisponi, L., Deiana, M., Dragatsis, I., Schlessinger, D., Pilia, G., Efstratiadis, A. Dev. Biol. (2002) [Pubmed]
  9. Glypicans are differentially expressed during patterning and neurogenesis of early mouse brain. Luxardi, G., Galli, A., Forlani, S., Lawson, K., Maina, F., Dono, R. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  10. Overgrowth syndromes and genomic imprinting: from mouse to man. Li, M., Squire, J.A., Weksberg, R. Clin. Genet. (1998) [Pubmed]
  11. Regulatory variation at glypican-3 underlies a major growth QTL in mice. Oliver, F., Christians, J.K., Liu, X., Rhind, S., Verma, V., Davison, C., Brown, S.D., Denny, P., Keightley, P.D. PLoS Biol. (2005) [Pubmed]
  12. Glypican-3 is a novel inhibitor of insulin-like growth factor signaling. Filmus, J., Song, H., Shi, W., Duenas Gonzalez, A., Kaya, M., Cano-Gauci, D. Medicina (B Aires) (1999) [Pubmed]
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