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Erschienen in: Medical Oncology 2/2012

01.06.2012 | Original Paper

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

verfasst von: 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

Erschienen in: Medical Oncology | Ausgabe 2/2012

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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.
Literatur
1.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat Ho M, Kim H. Glypican-3: a new target for cancer immunotherapy. Eur J Cancer. 2011;47:333–8.PubMedCrossRef Ho M, Kim H. Glypican-3: a new target for cancer immunotherapy. Eur J Cancer. 2011;47:333–8.PubMedCrossRef
22.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Zurück zum Zitat 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.
Metadaten
Titel
Expression of GPC3 protein and its significance in lung squamous cell carcinoma
verfasst von
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
Publikationsdatum
01.06.2012
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 2/2012
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-011-9973-1

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