Glypican-3 expression in Wilms tumor and hepatoblastoma

Our plain-English summary of Glypican-3 expression in Wilms tumor and hepatoblastoma, by J.A. Toretsky, N.L. Zitomersky, A.E. Eskenazi, et al (Journal of Pediatric Hematology/oncology, 2001).

The study

• Authors: J.A. Toretsky, N.L. Zitomersky, A.E. Eskenazi, R.W. Voigt, E.D. Strauch, C.C. Sun, R. Huber, S.J. Meltzer, D. Schlessinger
• Journal: Journal of Pediatric Hematology/oncology
• Published: 2001;23(8):496-9
• Cited by: 81 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Glypican-3 (GPC3) is a heparan sulfate proteoglycan. When it is disrupted, it causes the X-linked gigantism-overgrowth Simpson-Golabi-Behmel syndrome. Its involvement in growth control is consistent with recent reports that it can bind to growth factors, possibly including insulin-like growth factor 2. Further, it has been hypothesized that it may function as a tumor suppressor gene in breast and ovarian carcinomas and mesotheliomas.

Patients And Methods: RNA and protein were extracted from Wilms tumor and hepatoblastoma tissue samples and GPC3 levels were measured in these extracts by Northern blotting, reverse transcription polymerase chain reaction, and immunoblotting.

Results: In contrast to published results with carcinomas, high levels of GPC3 expression were found in Wilms tumor and hepatoblastoma. Low or undetectable expressions of this gene were found in normal tissue surrounding the tumor.

Conclusions: Increased expression of GPC3 in Wilms tumor and hepatoblastoma suggests a growth-promoting or neutral activity for this gene product rather than a growth-suppressive effect.

In plain English

This laboratory study did not examine asbestos or mesothelioma. Mesothelioma appears only in the background, where the authors cite earlier work suggesting that the gene glypican-3 (GPC3) might suppress tumor growth. The authors measured GPC3 RNA in childhood kidney tumors (Wilms tumor) and liver tumors (hepatoblastoma), and protein in Wilms tumors, comparing them with nearby normal tissue. Samples came from consecutive University of Maryland patients (1997 to 1999), plus extra hepatoblastoma samples from outside sources. Seven of eight Wilms tumors had high levels of GPC3 messenger RNA, while only one of five normal kidney specimens had detectable GPC3. One renal cell carcinoma had no detectable GPC3 by RT-PCR, which the authors described as lacking expression. Six of seven hepatoblastomas had more GPC3 than the adjoining liver. Protein and RNA results agreed in seven of nine tumor samples. Fetal kidney and liver also expressed GPC3. The authors concluded that the higher GPC3 in these tumors suggests the gene promotes growth or is neutral, rather than suppressing it. They noted their measurements showed relative, not absolute, levels, and that a functional model is needed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study measuring GPC3 RNA and protein expression in tumor tissue samples compared with adjacent normal tissue
• Who was studied: Tumor and adjacent normal tissue from consecutive patients at the University of Maryland, 1997 to 1999 (9 kidney-tumor samples in Table 1, including one renal cell carcinoma), plus additional hepatoblastoma samples from Dr. Julie Ross and the Cooperative Human Tissue Network (7 hepatoblastoma pairs in total)
• Exposure: No asbestos or other fiber exposure was studied. The study measured expression of the GPC3 gene in tumors.
• Main results:
  • Seven of eight Wilms tumors expressed high GPC3 mRNA levels, and only one of five normal kidney specimens expressed detectable GPC3
  • The authors described the one renal cell carcinoma sample as lacking GPC3 expression, even by RT-PCR (Table 1 scores it 0 by RT-PCR)
  • In Wilms tumor samples, RNA and protein results agreed in four of five paired samples and in seven of nine tumor samples overall
  • Six of seven hepatoblastomas expressed more GPC3 than the adjoining normal liver
  • Fetal liver and fetal kidney also expressed GPC3
• The authors' conclusion: The authors concluded that increased GPC3 expression in Wilms tumor and hepatoblastoma suggests a growth-promoting or neutral activity for the gene product rather than a growth-suppressive effect
• Limitations the authors state:
  • The authors could not fully explain the RNA and protein discordance in patient 2 because no additional patient material was available
  • Measurements show relative levels, not absolute quantities
  • One tumor/normal pair had partially degraded RNA that could not be used for Northern analysis
  • Further evaluation requires a functional model of GPC3

Topics

Medical terms in this study, explained in our Lexicon: Tumor Suppressor Gene, Carcinoma, Mesothelioma.

Related studies

• Pleural malignant mesothelioma following Wilms' tumor — M.B. Austin, R.E. Fechner, et al. (1986)
• Expression of the Wilms' tumor gene WT1 in human malignant mesothelioma cell lines and relationship to platelet-derived growth factor A and insulin-like growth factor 2 expression — A.W. Langerak, K.A. Williamson, et al. (1995)
• Unusual cases: melanomatosis and nephroblastomatosis treated with hyperthermic intraperitoneal chemotherapy — A. Hayes-Jordan, H. Green, et al. (2012)
• Embryonic ultrastructure as a guide in the diagnosis of tumors — G.R. Dickersin (1987)
• Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma — S. Cedrés, M.A. Montero, et al. (2014)
• Expression of genes coding for proteoglycans and Wilms' tumour susceptibility gene 1 (WT1) by variously differentiated benign human mesothelial cells — M. Gulyás, K. Dobra, et al. (1999)

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