Skip to main content
Top
Published in: Medical Oncology 2/2012

01-06-2012 | Original Paper

Expression of GPC3 protein and its significance in lung squamous cell carcinoma

Authors: Qiang Lin, Li-wen Xiong, Xu-feng Pan, Jun-feng Gen, Guo-liang Bao, Hui-fang Sha, Jiu-xian Feng, Chun-yu Ji, Ming Chen

Published in: Medical Oncology | Issue 2/2012

Login to get access

Abstract

The purpose of this study was to investigate GPC3 gene expression in lung squamous cell carcinoma tissue and its correlation with clinical and tumor characteristics. Using RT–PCR, the presence of GPC3 gene expression was detected in cancer tissue and adjacent normal tissue in 66 cases of lung squamous cell carcinoma and positive rates were calculated. Using Western blot, changes in GPC3 protein expression were detected in lung squamous cell carcinoma and adjacent normal tissues. The percentage of tissue samples expressing GPC3 mRNA was significantly higher in lung squamous cell carcinoma than in adjacent normal tissue (P < 0.05). This percentage was also significantly higher for cases with lymph node metastasis than for those without lymph node metastasis (P < 0.05). Further, the percentage of samples expressing GPC3 mRNA was higher with lowering degrees of tumor differentiation (P < 0.05). Rates of GPC3 expression were, however, independent of patient gender, age, and tumor size (P > 0.05). The expression of GPC3 protein in lung squamous cell carcinoma was significantly higher than that in adjacent normal tissues (P < 0.05). The expression in cases with lymph node metastasis was significantly higher than in those without lymph node metastasis (P < 0.05), and GPC3 protein expression increased with lowering degrees of tumor differentiation (P < 0.05). Further investigation is warranted for the association of initiation, development, invasion, and metastasis of disease.
Literature
1.
go back to reference Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2:89–99.PubMed Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2:89–99.PubMed
2.
go back to reference Gonzalez AD, Kaya M, Shi W, Song H, Testa JR, Penn LZ, Filmus J. OCI-5/GPC3, a glypican encoded by a gene that is mutated in the Simpson-Golabi-Behmel overgrowth syndrome, induces apoptosis in a cell line-specific manner. J Cell Biol. 1998;141:1407–14.PubMedCrossRef Gonzalez AD, Kaya M, Shi W, Song H, Testa JR, Penn LZ, Filmus J. OCI-5/GPC3, a glypican encoded by a gene that is mutated in the Simpson-Golabi-Behmel overgrowth syndrome, induces apoptosis in a cell line-specific manner. J Cell Biol. 1998;141:1407–14.PubMedCrossRef
3.
go back to reference Yamauchi N, Watanabe A, Hishinuma M, Ohashi K, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M, et al. The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol. 2005;18:1591–8.PubMed Yamauchi N, Watanabe A, Hishinuma M, Ohashi K, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M, et al. The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. Mod Pathol. 2005;18:1591–8.PubMed
4.
go back to reference Kandil D, Leiman G, Allegretta M, Evans M. Glypican-3 protein expression in primary and metastatic melanoma: a combined immunohistochemistry and immunocytochemistry study. Cancer Cytopathol. 2009;117:271–8.CrossRef Kandil D, Leiman G, Allegretta M, Evans M. Glypican-3 protein expression in primary and metastatic melanoma: a combined immunohistochemistry and immunocytochemistry study. Cancer Cytopathol. 2009;117:271–8.CrossRef
5.
go back to reference Oishi C, Baba T, Kubota Y, Shimotsuma Y, Kitamura K, Honma T, Ikegami A, Inokuchi M, Umeda T, Yoshida H, et al. Two cases of gastric cancer expressing Glypican 3, but producing AFP with different lectin affinity. Nippon Shokakibyo Gakkai Zasshi. 2009;106:805–12.PubMed Oishi C, Baba T, Kubota Y, Shimotsuma Y, Kitamura K, Honma T, Ikegami A, Inokuchi M, Umeda T, Yoshida H, et al. Two cases of gastric cancer expressing Glypican 3, but producing AFP with different lectin affinity. Nippon Shokakibyo Gakkai Zasshi. 2009;106:805–12.PubMed
6.
go back to reference Buchanan C, Stigliano I, Garay-Malpartida HM, Rodrigues Gomes L, Puricelli L, Sogayar MC, Bal de Kier Joffe E, Peters MG. Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3 K/Akt and p38MAPK signaling pathways. Breast Cancer Res Treat. 2010;119:559–74.PubMedCrossRef Buchanan C, Stigliano I, Garay-Malpartida HM, Rodrigues Gomes L, Puricelli L, Sogayar MC, Bal de Kier Joffe E, Peters MG. Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3 K/Akt and p38MAPK signaling pathways. Breast Cancer Res Treat. 2010;119:559–74.PubMedCrossRef
7.
go back to reference Maeda D, Ota S, Takazawa Y, Aburatani H, Nakagawa S, Yano T, Taketani Y, Kodama T, Fukayama M. Glypican-3 expression in clear cell adenocarcinoma of the ovary. Mod Pathol. 2009;22:824–32.PubMed Maeda D, Ota S, Takazawa Y, Aburatani H, Nakagawa S, Yano T, Taketani Y, Kodama T, Fukayama M. Glypican-3 expression in clear cell adenocarcinoma of the ovary. Mod Pathol. 2009;22:824–32.PubMed
8.
go back to reference Toretsky JA, Zitomersky NL, Eskenazi AE, Voigt RW, Strauch ED, Sun CC, Huber R, Meltzer SJ, Schlessinger D. Glypican-3 expression in Wilms tumor and hepatoblastoma. J Pediatr Hematol Oncol. 2001;23:496–9.PubMedCrossRef Toretsky JA, Zitomersky NL, Eskenazi AE, Voigt RW, Strauch ED, Sun CC, Huber R, Meltzer SJ, Schlessinger D. Glypican-3 expression in Wilms tumor and hepatoblastoma. J Pediatr Hematol Oncol. 2001;23:496–9.PubMedCrossRef
9.
go back to reference Murthy SS, Shen T, De Rienzo A, Lee WC, Ferriola PC, Jhanwar SC, Mossman BT, Filmus J, Testa JR. Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma. Oncogene. 2000;19:410–6.PubMedCrossRef Murthy SS, Shen T, De Rienzo A, Lee WC, Ferriola PC, Jhanwar SC, Mossman BT, Filmus J, Testa JR. Expression of GPC3, an X-linked recessive overgrowth gene, is silenced in malignant mesothelioma. Oncogene. 2000;19:410–6.PubMedCrossRef
10.
go back to reference Nakatsura T, Kageshita T, Ito S, Wakamatsu K, Monji M, Ikuta Y, Senju S, Ono T, Nishimura Y. Identification of glypican-3 as a novel tumor marker for melanoma. Clin Cancer Res. 2004;10:6612–21.PubMedCrossRef Nakatsura T, Kageshita T, Ito S, Wakamatsu K, Monji M, Ikuta Y, Senju S, Ono T, Nishimura Y. Identification of glypican-3 as a novel tumor marker for melanoma. Clin Cancer Res. 2004;10:6612–21.PubMedCrossRef
11.
go back to reference Peters MG, Farias E, Colombo L, Filmus J, Puricelli L, Bal de Kier Joffe E. Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model. Breast Cancer Res Treat. 2003;80:221–32.PubMedCrossRef Peters MG, Farias E, Colombo L, Filmus J, Puricelli L, Bal de Kier Joffe E. Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model. Breast Cancer Res Treat. 2003;80:221–32.PubMedCrossRef
12.
go back to reference Lin H, Huber R, Schlessinger D, Morin PJ. Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res. 1999;59:807–10.PubMed Lin H, Huber R, Schlessinger D, Morin PJ. Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res. 1999;59:807–10.PubMed
13.
go back to reference Powell CA, Xu G, Filmus J, Busch S, Brody JS, Rothman PB. Oligonucleotide microarray analysis of lung adenocarcinoma in smokers and nonsmokers identifies GPC3 as a potential lung tumor suppressor. Chest. 2002;121(3 Suppl):6S–7S.PubMedCrossRef Powell CA, Xu G, Filmus J, Busch S, Brody JS, Rothman PB. Oligonucleotide microarray analysis of lung adenocarcinoma in smokers and nonsmokers identifies GPC3 as a potential lung tumor suppressor. Chest. 2002;121(3 Suppl):6S–7S.PubMedCrossRef
14.
go back to reference Kim H, Xu GL, Borczuk AC, Busch S, Filmus J, Capurro M, Brody JS, Lange J, D’Armiento JM, Rothman PB, et al. The heparan sulfate proteoglycan GPC3 is a potential lung tumor suppressor. Am J Respir Cell Mol Biol. 2003;29:694–701.PubMedCrossRef Kim H, Xu GL, Borczuk AC, Busch S, Filmus J, Capurro M, Brody JS, Lange J, D’Armiento JM, Rothman PB, et al. The heparan sulfate proteoglycan GPC3 is a potential lung tumor suppressor. Am J Respir Cell Mol Biol. 2003;29:694–701.PubMedCrossRef
15.
go back to reference Baumhoer D, Tornillo L, Stadlmann S, Roncalli M, Diamantis EK, Terracciano LM. Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4, 387 tissue samples. Am J Clin Pathol. 2008;129:899–906.PubMedCrossRef Baumhoer D, Tornillo L, Stadlmann S, Roncalli M, Diamantis EK, Terracciano LM. Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4, 387 tissue samples. Am J Clin Pathol. 2008;129:899–906.PubMedCrossRef
17.
go back to reference Buchanan C, Stigliano I, Garay-Malpartida HM, Rodrigues Gomes L, Puricelli L, Sogayar MC, Bal de Kier Joffe E, Peters MG. Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3 K/Akt and p38MAPK signaling pathways. Breast Cancer Res Treat. 2010;119:559–74.PubMedCrossRef Buchanan C, Stigliano I, Garay-Malpartida HM, Rodrigues Gomes L, Puricelli L, Sogayar MC, Bal de Kier Joffe E, Peters MG. Glypican-3 reexpression regulates apoptosis in murine adenocarcinoma mammary cells modulating PI3 K/Akt and p38MAPK signaling pathways. Breast Cancer Res Treat. 2010;119:559–74.PubMedCrossRef
18.
go back to reference Zynger DL, Dimov ND, Luan C, Teh BT, Yang XJ. Glypican 3: a novel marker in testicular germ cell tumors. Am J Surg Pathol. 2006;30:1570–5.PubMedCrossRef Zynger DL, Dimov ND, Luan C, Teh BT, Yang XJ. Glypican 3: a novel marker in testicular germ cell tumors. Am J Surg Pathol. 2006;30:1570–5.PubMedCrossRef
19.
go back to reference Akutsu N, Yamamoto H, Sasaki S, Taniguchi H, Arimura Y, Imai K. Shinomura Y: Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma. World J Gastroenterol. 2010;16:3521–8.PubMedCrossRef Akutsu N, Yamamoto H, Sasaki S, Taniguchi H, Arimura Y, Imai K. Shinomura Y: Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma. World J Gastroenterol. 2010;16:3521–8.PubMedCrossRef
20.
go back to reference Suzuki M, Sugimoto K, Tanaka J, Tameda M, Inagaki Y, Kusagawa S, Nojiri K, Beppu T, Yoneda K, Yamamoto N, et al. Up-regulation of glypican-3 in human hepatocellular carcinoma. Anticancer Res. 2010;30:5055–61.PubMed Suzuki M, Sugimoto K, Tanaka J, Tameda M, Inagaki Y, Kusagawa S, Nojiri K, Beppu T, Yoneda K, Yamamoto N, et al. Up-regulation of glypican-3 in human hepatocellular carcinoma. Anticancer Res. 2010;30:5055–61.PubMed
21.
22.
go back to reference Zhu ZW, Friess H, Wang L, Abou-Shady M, Zimmermann A, Lander AD, Korc M, Kleeff J, Buchler MW. Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut. 2001;48:558–64.PubMedCrossRef Zhu ZW, Friess H, Wang L, Abou-Shady M, Zimmermann A, Lander AD, Korc M, Kleeff J, Buchler MW. Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut. 2001;48:558–64.PubMedCrossRef
23.
go back to reference Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12:241–7.PubMedCrossRef Pilia G, Hughes-Benzie RM, MacKenzie A, Baybayan P, Chen EY, Huber R, Neri G, Cao A, Forabosco A, Schlessinger D. Mutations in GPC3, a glypican gene, cause the Simpson-Golabi-Behmel overgrowth syndrome. Nat Genet. 1996;12:241–7.PubMedCrossRef
24.
go back to reference Umezu T, Shibata K, Kajiyama H, Yamamoto E, Nawa A, Kikkawa F. Glypican-3 expression predicts poor clinical outcome of patients with early-stage clear cell carcinoma of the ovary. J Clin Pathol. 2010;63:962–6.PubMedCrossRef Umezu T, Shibata K, Kajiyama H, Yamamoto E, Nawa A, Kikkawa F. Glypican-3 expression predicts poor clinical outcome of patients with early-stage clear cell carcinoma of the ovary. J Clin Pathol. 2010;63:962–6.PubMedCrossRef
25.
go back to reference Xiang YY, Ladeda V, Filmus J. Glypican-3 expression is silenced in human breast cancer. Oncogene. 2001;20:7408–12.PubMedCrossRef Xiang YY, Ladeda V, Filmus J. Glypican-3 expression is silenced in human breast cancer. Oncogene. 2001;20:7408–12.PubMedCrossRef
26.
go back to reference Song HH, Shi W, Xiang YY, Filmus J. The loss of glypican-3 induces alterations in Wnt signaling. J Biol Chem. 2005;280:2116–25.PubMedCrossRef Song HH, Shi W, Xiang YY, Filmus J. The loss of glypican-3 induces alterations in Wnt signaling. J Biol Chem. 2005;280:2116–25.PubMedCrossRef
27.
go back to reference Lee EH, Chari R, Lam A, Ng RT, Yee J, English J, Evans KG, Macaulay C, Lam S, Lam WL. Disruption of the non-canonical WNT pathway in lung squamous cell carcinoma. Clin Med Oncol. 2008;2:169–79. Lee EH, Chari R, Lam A, Ng RT, Yee J, English J, Evans KG, Macaulay C, Lam S, Lam WL. Disruption of the non-canonical WNT pathway in lung squamous cell carcinoma. Clin Med Oncol. 2008;2:169–79.
Metadata
Title
Expression of GPC3 protein and its significance in lung squamous cell carcinoma
Authors
Qiang Lin
Li-wen Xiong
Xu-feng Pan
Jun-feng Gen
Guo-liang Bao
Hui-fang Sha
Jiu-xian Feng
Chun-yu Ji
Ming Chen
Publication date
01-06-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9973-1

Other articles of this Issue 2/2012

Medical Oncology 2/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.