Expression of OCI-5/Glypican 3 during Intestinal Morphogenesis: Regulation by Cell Shape in Intestinal Epithelial Cells

Li, Madeline; Choo, Bok Ai; Wong, Zeu-Ming; Filmus, Jorge; Buick, Roger

doi:10.1006/excr.1997.3629

Cited by 41 publications

(18 citation statements)

References 34 publications

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“…Glypican-3 (GPC3) was originally isolated as a developmentally regulated transcript from the rat intestine, and was later identified as a GPI (glycosyl phosphatidyl inositol)-linked heparan sulfate proteoglycan with a wider expression (4). In vivo, it was found to be predominantly expressed in the mesoderm and mesoderm-derived tissues, and too much lesser extent in endodermal-and ectodermal-derived tissues (5).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of glypican-3 expression via RNA interference influences the growth and invasive ability of the MHCC97-H human hepatocellular carcinoma cell line

Ruan

Liu²,

Chen³

et al. 2011

Int J Mol Med

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Abstract. Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is found to be overexpressed in hepatocellular carcinoma (HCC). The purpose of the present study was to investigate the possible role of GPC3 in the development of HCC. In this study, RNA interference (RNAi) with a GPC3 small hairpin RNA (GPC3 shRNA) was used to identify the effects of GPC3 on the regulation of malignant behaviors of HCC. MHCC97-H, a highly metastatic human HCC cell line in which GPC3 mRNA and protein levels were detected as the highest among the 4 HCC cell lines assessed in this study, and was thus selected as a cell model for in vitro and in vivo experiments. The results showed that down-regulation of GPC3 can significantly inhibit the proliferative and invasive ability of MHCC97-H. Compared with the parental HCC cells, GPC3-silenced cells exhibited attenuated capacities in developing tumors in nude mice, while the growth of tumor xenografts derived from these cells dramatically regressed. In conclusion, our results suggest that GPC3 contributes to the proliferation and metastasis of HCC and that it may be a potential molecular target for HCC treatment.

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Section: Introductionmentioning

confidence: 99%

Inhibition of glypican-3 expression via RNA interference influences the growth and invasive ability of the MHCC97-H human hepatocellular carcinoma cell line

Ruan

Liu²,

Chen³

et al. 2011

Int J Mol Med

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“…This signaling pathway may be of particular relevance to neuroblastoma cells because they arise from migratory neural crest-derived neuroblasts (11)(12)(13). Glypicans play an important role in developmental morphogenesis and are known to be modulators for the Wnt signaling pathway (14)(15)(16)(17). It has been shown that GPC3, another member of the glypican family, may function as a coreceptor for Wnt and facilitate the Wnt/Frizzled binding in hepatocellular carcinoma cells (18,19).…”

mentioning

confidence: 99%

Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

Hewitt

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

109

126

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Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/ β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma.glypican | neuroblastoma | single-domain antibody | chimeric antigen receptor T-cell therapy | immunotoxin

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“…The con¯uence-dependent induction of OCI-5 in IEC-18 cells was previously analysed on a cellular level and shown to be a function of the change from a¯at, elongated morphology to the more rounded, compact cell shape associated with high cell densities (Li et al, 1997). A role for cell shape in regulating developmental gene expression is increasingly recognized (Ingber, 1993;Ingber et al, 1994) and is likely to be found in genes which are expressed during tissue morphogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of OCI-5 during intestinal development in the rat is temporally and spatially regulated (Li et al, 1997). The OCI-5 transcript can be detected both in endoderm-and mesenchyme-derived cells in a phased manner related to age and proximaldistal position.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of OCI-5/Glypican 3: elongation control of confluence-dependent induction

Pullano

Heng

et al. 1997

Oncogene

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OCI-5/Glypican 3, a member of the glypican family of proteoglycans, is the defective gene in the SimpsonGolabi-Behmel overgrowth syndrome. OCI-5 expression is developmentally regulated in the intestinal epithelium, and the mechanism of its regulation was studied in the rat intestinal epithelial cell line IEC-18. A large induction of OCI-5 transcript and protein was observed at high cell density. Among other glypican family members, k-glypican also exhibited a con¯uence-dependent induction in select cell types. Nuclear run-on analysis indicated that cell-density regulation of OCI-5 occurs at the level of transcription. The rat and mouse OCI-5 promoters were cloned and found to be highly conserved, located within CpG islands and contain regions of alternating purine and pyrimidine residues. No TATA-box or recognizable INR element was observed. Consensus binding sites for AP-2, SP-1, zeste and NF-1/CTF are conserved across human, mouse and rat promoters. 5' deletion mapping of the rat promoter identi®ed regions which enhance and repress promoter activity, with no apparent con¯uence-dependence or tissue-speci®city. Nuclear run-on analysis probing dierent regions of the gene suggests that elongation control plays a role in the induction of OCI-5 by con¯uence.

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Expression of OCI-5/Glypican 3 during Intestinal Morphogenesis: Regulation by Cell Shape in Intestinal Epithelial Cells

Cited by 41 publications

References 34 publications

Inhibition of glypican-3 expression via RNA interference influences the growth and invasive ability of the MHCC97-H human hepatocellular carcinoma cell line

Inhibition of glypican-3 expression via RNA interference influences the growth and invasive ability of the MHCC97-H human hepatocellular carcinoma cell line

Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

Transcriptional regulation of OCI-5/Glypican 3: elongation control of confluence-dependent induction

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