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Overexpression of Cap43 gene in supraglottic laryngeal squamous cell carcinoma

Published online by Cambridge University Press:  22 May 2009

X Li
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Shanghai Children's Hospital, Shanghai Jiaotong University, China Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
K Sakamoto
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
Y Takahashi
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
T Nakashima*
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume, Japan
*
Address for correspondence: Dr Tadashi Nakashima, Department of Otolaryngology-Head and Neck Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan. Fax: +81 942 37 1200 E-mail: [email protected]

Abstract

Objective:

This study aimed to determine the expression of the Cap43 gene in supraglottic laryngeal squamous cell carcinoma, and to evaluate any correlation between Cap43 gene expression and tumour-associated macrophage infiltration.

Methods:

Four human head and neck squamous cell carcinoma cell lines were cultured (Hep2, KB, Ca9-22 and HSC-3) and expression of the Cap43 gene was analysed by Western blotting. In addition, paraffin-embedded samples of supraglottic laryngeal squamous cell carcinoma and normal supraglottic laryngeal mucosa from 84 patients were analysed immunohistochemically using antibodies to Cap43 and cluster of differentiation 68 glycoprotein. Patients' clinical status was compared with their immunohistochemical results.

Results:

All four head and neck squamous cell carcinoma cell lines exhibited Cap43 expression. The Hep2, Ca9-22 and HSC-3 cells showed a markedly higher level of Cap43 protein than the KB cells. A statistically significant difference was found in Cap43 expression, comparing different differentiation levels and comparing different metastasis stages, for supraglottic squamous cell carcinoma. The number of tumour-associated macrophages correlated with expression of Cap43, not only in the tumour area (r = 0.3708, p = 0.0005) but also in the peritumour area (r = 0.2847, p = 0.0087).

Conclusion:

In supraglottic laryngeal squamous cell carcinoma, overexpression of the Cap43 gene is associated with tumour differentiation and acts an important suppressive factor in the process of tumour metastasis. The Cap43 gene may be a cancer-specific marker. High expression of the Cap43 gene appeared to correlate with infiltration of tumour-associated macrophages.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2009

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References

1Zoroddu, MA, Peana, M, Kowalik-Jankowska, T, Kozlowski, H, Costa, M. Nickel (II) binding to Cap43 protein fragments. J Inorg Biochem 2004;98:931–9Google Scholar
2Salnikow, K, Kluz, T, Costa, M. Role of Ca2+ in the regulation of nickel-inducible Cap43 gene expression. Toxicol Appl Pharmacol 1999;160:127–32Google Scholar
3Zhou, D, Salnikow, K, Costa, M. Cap43, a novel gene specifically induced by Ni2+ compounds. Cancer Res 1998;58:2182–9Google ScholarPubMed
4Lachat, P, Shaw, P, Gebhard, S, van Belzen, N, Chaubert, P, Bosman, FT. Expression of NDRG1, a differentiation-related gene, in human tissues. Histochem Cell Biol 2002;118:399408Google Scholar
5Guan, RJ, Ford, Hl, Fu, Y, Li, Y, Shaw, LM, Pardee, AB. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res 2000;60:749–55Google Scholar
6Piquemal, D, Joulia, D, Balaguer, P, Basset, A, Marti, J, Commes, T. Differential expression of the RTP/Drg1/Ndr1 gene product in proliferating and growth arrested cells. Biochim Biophys Acta 1999;1450:364–73CrossRefGoogle ScholarPubMed
7Kurdistani, SK, Arizti, P, Reimer, CL, Sugrue, MM, Aaronson, SA, Lee, SW. Inhibition of tumour cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage. Cancer Res 1998;58:4439–44Google ScholarPubMed
8Bandyopadhyay, S, Pai, SK, Hirota, S, Hosobe, S, Takano, Y, Saito, K et al. Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene 2004;23:5675–81Google Scholar
9Nishie, A, Masuda, K, Otsubo, M, Migita, T, Tsuneyoshi, M, Kohno, K et al. High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas. Clin Cancer Res 2001;7:2145–51Google Scholar
10Session, RB, Harrison, LB, Forastiere, AAW. Tumors of the larynx and hypopharynx. In: DeVita, VTJ, Hellman, S, Rosenberg, S, eds. Cancer: Principles and Practice of Oncology. Philadelphia: JB Lippincott, 2001;861–86Google Scholar
11Thawley, S, Panje, W, Batsakis, J, Lindberg, R. Comprehensive management of head and neck tumors. Philadelphia: WB Saunders, 1999Google Scholar
12Salnikow, K, Davidson, T, Costa, M. The role of hypoxia-inducible signaling pathway in nickel carcinogenesis. Environ Health Perspect 2002;110(suppl 5):831–4CrossRefGoogle ScholarPubMed
13Funakoshi, T, Inoue, T, Shinmada, H, Kojima, SThe mechanism of nickel uptake by rat primary hepatocyte cultures: role of calcium channels. Toxicology 1197;124:21–6Google Scholar
14Cangul, H, Salnikow, K, Yee, H, Zagzag, D, Commes, T, Costa, M. Enhanced overexpression of an HIF-1/hypoxia-related protein in cancer cells. Environ Health Perspect 2002;110(suppl 5):783–8CrossRefGoogle ScholarPubMed
15Bandyopadhyay, S, Pai, SK, Hirota, S, Hosobe, S, Tsukada, T, Miura, K et al. PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer. Cancer Res 2004;64:7655–60CrossRefGoogle ScholarPubMed
16Dong, Z, Arnold, RJ, Yang, Y, Park, MH, Hmcirova, P, Mechref, Y et al. Modulation of differentiation-related gene 1 expression by cell cycle blocker mimosine, revealed by proteomic analysis. Mol Cell Proteomics 2005;4:9931001CrossRefGoogle ScholarPubMed
17Ryan, HE, Lo, J, Johnson, RS. HIF-1α is required for solid tumor formation and embryonic vascularization. EMBO J 1998;17:3005–15Google Scholar
18Hockel, M, Schlenger, K, Aral, B, Mitze, M, Schaffer, U, Vaupel, P. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 1996;56:4509–15Google ScholarPubMed
19Bandyopadhyay, S, Pai, SK, Gross, SC, Hirota, S, Hosobe, S, Miura, K et al. The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res 2003;63:1731–6Google ScholarPubMed
20Kuwano, M, Fukushi, J, Okamoto, M, Nishie, A, Goto, H, Ishibashi, T et al. Angiogenesis factors. Intern Med 2001;40:565–72Google Scholar
21Ono, M, Torisu, H, Fukushi, J, Nishie, A, Kuwano, M. Biological implications of macrophage infiltration in human tumour angiogenesis. Cancer Chemother Pharmacol 1999;43:6971CrossRefGoogle Scholar
22Coussens, LM, Werb, Z. Inflammation and cancer. Nature 2002;420:860–7CrossRefGoogle ScholarPubMed