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Research Article
Wei Cheng
Department of Pathology, Kee-Lung Hospital, Ministry of Health and Welfare
Corresponding Author
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Background: Glypican-3 (GPC3) mRNA was more frequently overexpressed in women and patients with invasive HCC. We explore possible molecular mechanisms of the effect of GPC3 on growth factor receptor-bound protein 10 (Grb10) and insulin-like growth factor 1 receptor (IGF-1R) interaction of tumor invasion in women.
Methods: For in vitro experiments, GPC3 and pertinent mutants were transfected, and Western blotting (HEK293T cells), confocal microscopy (HeLa and PLC-PRF-5 cells), luciferase assays for AP-1 reporter activities (NIH3T3 and HuH-7 cells), gelatin zymography (PLC-PRF-5 cells) and cell culture in 3D collagen I gels (NIH3T3 and R- cells) were performed. For in vivo experiments, GPC3 and IGF-1R coexpression was evaluated in hepatocellular carcinoma clinical samples.
Results: We found that interaction of IGF-1R with Grb10 was hindered by GPC3, and GPC3 causes IGF-1R colocalization with Grb10 to a lesser extent after IGF-1 stimulation; moreover, it promoted IGF-1-stimulated AP-1 activation and matrix metalloproteinase -2 and 9 (MMP-2 and MMP-9) secretion in vitro, which seemingly play a role in tumor invasion or recurrence. Further, gender differences existed among patients with hepatocellular carcinoma in terms of GPC3 and IGF-1R coexpression in vivo.
Conclusions: We believe that a more intensive surveillance of GPC3 expression in female patients with hepatocellular carcinoma should contribute to the prediction of recurrence, and this may highlight new strategies for treating hepatocellular carcinoma in women.
Keywords
glypican-3 (GPC3), insulin-like growth factor 1 receptor (IGF-1R), growth factor receptor-bound protein 10 (Grb10), hepatocellular carcinoma (HCC)
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Wei Cheng
Department of Pathology, Kee-Lung Hospital, Ministry of Health and Welfare
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 17 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Glypican-3 (GPC3) mRNA was more frequently overexpressed in women and patients with invasive HCC. We explore possible molecular mechanisms of the effect of GPC3 on growth factor receptor-bound protein 10 (Grb10) and insulin-like growth factor 1 receptor (IGF-1R) interaction of tumor invasion in women.
Methods: For in vitro experiments, GPC3 and pertinent mutants were transfected, and Western blotting (HEK293T cells), confocal microscopy (HeLa and PLC-PRF-5 cells), luciferase assays for AP-1 reporter activities (NIH3T3 and HuH-7 cells), gelatin zymography (PLC-PRF-5 cells) and cell culture in 3D collagen I gels (NIH3T3 and R- cells) were performed. For in vivo experiments, GPC3 and IGF-1R coexpression was evaluated in hepatocellular carcinoma clinical samples.
Results: We found that interaction of IGF-1R with Grb10 was hindered by GPC3, and GPC3 causes IGF-1R colocalization with Grb10 to a lesser extent after IGF-1 stimulation; moreover, it promoted IGF-1-stimulated AP-1 activation and matrix metalloproteinase -2 and 9 (MMP-2 and MMP-9) secretion in vitro, which seemingly play a role in tumor invasion or recurrence. Further, gender differences existed among patients with hepatocellular carcinoma in terms of GPC3 and IGF-1R coexpression in vivo.
Conclusions: We believe that a more intensive surveillance of GPC3 expression in female patients with hepatocellular carcinoma should contribute to the prediction of recurrence, and this may highlight new strategies for treating hepatocellular carcinoma in women.
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This is a list of supplementary files associated with this preprint. Click to download.
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