Study of sialidase activity to evaluate malignant potential of carcinoma cells

Research Project

Project/Area Number	10671151
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 Syukichi Graduate Sch. of Medicine, Tohoku Univ., Research Associate, 大学院・医学系研究科, 助手 (50282075)
Co-Investigator(Kenkyū-buntansha)	TERASAWA Takayuki Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (10292319) SAYAMA Junzo Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (60292322) SHINEHA Ryuzaburo Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (20192106) ANDO Kenjiro Tohoku University Hospital, Research Associate, 医学部・附属病院, 助手 (40261614) 菅原弘光東北大学, 医学部附属病院, 助手 (80302123)
Project Period (FY)	1998 – 1999
Project Status	Completed(Fiscal Year 1999)
Budget Amount *help	¥3,000,000 (Direct Cost : ¥3,000,000) Fiscal Year 1999 : ¥1,000,000 (Direct Cost : ¥1,000,000) Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Keywords	sialidase / sialylation / B16 melanoma / colon 26 / metastatic potential / 食道癌 / 悪性度評価
Research Abstract	Alterations in sialylation have been found to be closely associated with metastatic potential. To elucidate how such aberrant sialylation occurs in cancer cells and why such changes affect metastasis, we have been studying sialidase expression in metastatic cells. In our previous studies murine tissues were found to contain at least four types of sialidase differing in subcellular location and enzymatic and immunological properties. Metastatic potential was found to be inversely correlated with lysosomal matrix-type sialidase activity in transformed rat 3Y1 cell lines. We also presented evidence suggesting an important role for sialidase in highly metastatic and invasive B16 melanoma variants, which exhibited decreased pulmonary metastasis on transfection of a cytosolic sialidase cDNA, with an associated decrease in GM3 content. To investigate further about sialidases and other target molecules in metastatic cells, we used mouse B16 melanoma and colon 26 cell lines. Relation between endogenous sialidase expression and metastatic potential were assessed in three B16 melanoma variants with different metastatic ability and colon 26 cell line. Highly metastatic cell line NL 17 (derivative of colon 26) was transfected with cytosolic sialidase cDNA, and the effect of cytosolic sialidase expression was studied. Results 1. Lysosomal sialidase activity inversely correlate with metastatic potential. 2. When highly metastatic cell were transfected with cytosolic sialidase, the metastatic potential was suppressed. And this suppression was mainly due to decrease of cell mobility and ability of invasion. 3. One of the target molecules of cytosolic and plasma membrane sialidase was suggested to be GM3, and GM3 level was increased in highly metastatic cell lines.