Study of sialidase expression in melanoma cell line and esophageal cancers

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: TOHOKU University
• Principal Investigator: MIYAZAKI Shukichi Tohoku Univ. Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (50282075)
• Co-Investigator(Kenkyū-buntansha): SUGAWARA Koh Tohoku Univ. School of Medicine Hospital, Research Associate, 医学部・附属病院, 助手 (30323025) ; MIYATA Goh Tohoku Univ. School of Medicine Hospital, Research Associate, 医学部・附属病院, 助手 (60282076)
• Project Period (FY): 2000 – 2001
• Keywords: Esophageal cancer / Sialidase / Metastatic potential / Gene therapy / sialylation

Research Abstract

Alteration in sialylation have been found to be closely associated with metastatic potential of derivatives from colon cancer cell line. In this study we studied the expression of sialidase in esophageal cancers and checked the correlation between sialidase levels and clinicopathological parameters of esophageal cancers to evaluate the usefulness of sialidase level as a parameter of malignant potential in esophageal cancer. We measured the sialidase leves of esophageal cancers by quantitative RT-PCR and compared with those of normal esophageal mucosa. As the results the average level of lysosomal sialidase was four times higher and the average level of cytosolic sialidase was two times higher in esophageal cancers than normal esophageal mucosa. These changes were also confirmed by enzymatic analysis. However, so far, there were no correlations between these data and the clinicopathological parameters in esophageal cancers.
On the other hand, in this study we also investigated the possibility of gene therapy using sialidase gene transfection.
We transfected the lysosomal sialidase gene to B16BL cell, which is the highly invasive and metastatic derivative from mouse melanoma cell line B16. We obtained four transformed stable cell lines and analyzed the effect of gene transfection on the metastatic potential and the malignant characters.
The results are
1) The expression of lysosomal sialidase suppress the lung metastases of B16BL cells.
2) This suppression was caused mainly by the decrease of anchorage independent growth.
3) Apoptosis increased in certain conditions.
4) One of the target molecules of lyaosomal sialidase was 83 kD glycoprotein.