Cancer Res Treat.  2005 Dec;37(6):360-364.

Overexpression of Metastatic Tumor Antigen in Osteosarcoma: Comparison between Conventional High-Grade and Central Low-Grade Osteosarcoma

Affiliations
  • 1Department of Pathology, College of Medicine, Hallym University, Anyang, Korea.
  • 2MyGene Bioscience Institute, Seoul, Korea.
  • 3Servizio di Anatomia Patologica, Istituto Ortopedico Rizzoli, Bologna, Italy.
  • 4Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Korea. ykpark@khmc.or.kr

Abstract

PURPOSE
The metastatic tumor antigen (MTA) gene is a recently identified metastasis-associated gene which has implications in the signal transduction or regulation of gene expression. However, the expression of MTA in osteosarcoma and its potential relationship with metastasis have not been examined, forming the basis of this study. MATERIALS AND METHODS: We compared the expression levels of the MTA1 protein between 32 cases of high- grade osteosarcomas and 21 cases of low-grade osteosarcomas by immunohistochemistry. In addition, the mRNA expression levels of MTA1, 2, 3 in these osteosarcoma cell lines and control fibroblasts were evaluated by real-time quantitative PCR. RESULTS: MTA1 immunoreactivity was present in 81.25% of high-grade osteosarcoma specimens. Its expression was predominantly localized to the nucleus or cytoplasm of osteosarcoma cells. Thirteen (86.6%) of 15 patients who died of osteosarcomas displayed strong MTA1 expression. Both primary bone and pulmonary metastatic lesions exhibited MTA1 expression. All low- grade osteosarcomas were negative for MTA1 except for focal weak reactivity in two cases. The tested high-grade osteosarcoma cell lines showed marked amplification of MTA1 and MTA2 mRNA compared to control cells. CONCLUSION: These results suggest that MTA might be involved in the progression of high-grade osteosarcoma, particularly in hematogenous metastasis of osteosarcoma.

Keyword

Metastatic tumor antigen (MTA); Osteosarcoma

MeSH Terms

Cell Line
Cytoplasm
Fibroblasts
Gene Expression Regulation
Humans
Immunohistochemistry
Neoplasm Metastasis
Osteosarcoma*
Polymerase Chain Reaction
RNA, Messenger
Signal Transduction
Pemetrexed
RNA, Messenger

Figure

  • Fig. 1 Immunohistochemistry for MTA1 in primary bone lesion of conventional high-grade osteosarcoma. Diffuse, strong expression was noted in the nucleus and cytoplasm of irregular pleomorphic tumor cells (original magnification, ×200).

  • Fig. 2 Immunohistochemistry for MTA1 in pulmonary metastatic tumor sample of high-grade osteosarcoma (original magnification, ×200).

  • Fig. 3 Immunohistochemistry for MTA1 in low-grade central osteosarcoma. All the tumor cells were negative (original magnification, ×200).

  • Fig. 4 Amplification curves for the MTA1 mRNA in osteosarcoma cell lines and control fibroblast by real-time quantitative PCR. All three osteosarcoma cell lines showed an average 8-fold higher amplification of MTA1 mRNA compared to the control.


Reference

1. DeMarzo AM, Nelson WG, Isaacs WB, Epstein JI. Pathological and molecular aspects of prostate cancer. Lancet. 2003; 361:955–964. PMID: 12648986.
Article
2. Dear TN, Ramshaw IA, Kefford RF. Differential expression of a novel gene, WDNM1, in nonmetastatic rat mammary adenocarcinoma cells. Cancer Res. 1988; 48:5203–5209. PMID: 3136918.
3. Phillips SM, Bendall AJ, Ramshaw IA. Isolation of gene associated with high metastatic potential in rat mammary adenocarcinomas. J Natl Cancer Inst. 1990; 82:199–203. PMID: 2296049.
Article
4. Sasaki H, Moriyama S, Nakashima Y, Kobayashi Y, Yukiue H, Kaji M, et al. Expression of the MTA1 mRNA in advanced lung cancer. Lung Cancer. 2002; 35:149–154. PMID: 11804687.
Article
5. Toh Y, Oki E, Oda S, Tokunaga E, Ohna S, Maehara Y, et al. Overexpression of the MTA1 gene in gastrointestinal carcinomas: correlation with invasion and metastasis. Int J Cancer. 1997; 74:459–463. PMID: 9291440.
6. Iguchi H, Imura G, Toh Y, Ogata Y. Expression of MTA1, a metastasis-associated gene with histone deacetylase activity in pancreatic cancer. Int J Oncol. 2000; 16:1211–1214. PMID: 10811997.
Article
7. Toh Y, Pencil SD, Nicolson GL. A novel candidate metastasis-associated gene, mta1, differentially expressed in highly metastatic mammary adenocarcinoma cell lines. J Biol Chem. 1994; 269:22958–22963. PMID: 8083195.
8. Xue Y, Wong J, Moreno GT, Young MK, Cote J, Wang W. NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities. Mol Cell. 1998; 2:851–861. PMID: 9885572.
Article
9. Mahoney MG, Simpson A, Jost M, Noe M, Kari C, Pepe D, et al. Metastasis-associated protein (MTA) 1 enhances migration, invasion, and anchorage-independent survival of immortalized human keratinocytes. Oncogene. 2002; 21:2161–2170. PMID: 11948399.
10. Moon WS, Chang K, Tarnawski AS. Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: Relationship to vascular invasion and estrogen receptor-α. Hum Pathol. 2004; 35:424–429. PMID: 15116322.
Article
11. Sasaki H, Yukiue H, Kobayashi Y, Nakashima Y, Kaji M, Fukai I, et al. Expression of the MTA1 mRNA in thymoma patients. Cancer Lett. 2001; 174:159–163. PMID: 11689291.
Article
12. Hofer MD, Kuefer R, Varambally S, Li H, Ma J, Shapiro GI, et al. The role of metastasis-associated protein 1 in prostate cancer progression. Cancer Res. 2004; 64:825–829. PMID: 14871807.
Article
13. Toh Y, Kuninaka S, Endo K, Oshiro T, Ikeda Y, Nakashima H, et al. Molecular analysis of a candidate metastasis-associated gene, MTA1: possible interaction with histone deacetylase 1. J Exp Clin Cancer Res. 2000; 19:105–111. PMID: 10840944.
14. Toh Y, Ohga T, Endo K, Adachi E, Kusumoto H, Haraguchi M, et al. Expression of the metastasis-associated MTA1 protein and its relationship to deacetylation of the histone H4 in esophageal squamous cell carcinomas. Int J Cancer. 2004; 110:362–367. PMID: 15095300.
Article
15. Nicolson G, Nawa A, Toh Y, Taniguchi S, Nishimori K, Moustafa A. Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation. Clin Exp Metastasis. 2003; 20:19–24. PMID: 12650603.
16. Zhang Y, Leroy G, Seelig HP, Lane WS, Reinberg D. The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities. Cell. 1998; 95:279–289. PMID: 9790534.
Article
17. Yoshida M, Horinouchi S, Beppu T. Trichostatin A and trapoxin: novel chemical probes for the role of histone acetylation in chromatin structure and function. Bioessays. 1995; 17:423–430. PMID: 7786288.
Article
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