Project/Area Number |
10671182
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Osaka University |
Principal Investigator |
NAKAMORI Shoji Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (70294080)
|
Co-Investigator(Kenkyū-buntansha) |
DONO Keizo Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (60283769)
SAKON Masato Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助教授 (40170659)
ARIYOSHI Hideo Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (60294055)
UMESHITA Kouji Osaka University Hospital, Osaka University, Assistant Professot, 医学部・附属病院, 助手 (60252649)
NAGANO Hiroaki Graduate School of Medicine, Osaka University, Assistant Professot, 医学系研究科, 助手 (10294050)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | Invasion / Endothelial cell / Retraction / FAK / Phosphorylation / Rho / Pancreatic Cancer / 癌転移 / 蛋白リン酸化 / 血管内皮細胞開裂 / pp125FAK |
Research Abstract |
When cancer cell permeates to the endothelial cell layer, endothelial cells should retract. We established assay system to measure quantitatively endothelial cell retraction activity and fonud that the endothelial cell retraction activity existed for human cancer cell culture supernatant over the 10 types using culture cell experimental system. Using pancreatic carcinoma cell line PSN-1 of which the endothelial cell retraction activity is the strongest, mechanisms of signal transduction during the endothelial cell retraction was examined. Addition of conditioned medium (CM) of PSN-1 cell culture induced decrease of phosphorylation of 120〜130Kd protein in the endothelial cell, and it was recognized that the protein with the decrease of phosphorylation is focal adhesion kinase that is involved in the intracellular skeleton control. To examine involvement of change of intracellular calcium level in the decrease of phosphorylation of 120〜130Kd protein, we observed intracellular calcium level in the endothelial cells by the confocal laser microscope. Addition of CM did not induced any change of intracellular calcium level in the endothelial cells. However, the change of intracellular calcium levels in endothelial cells was increased soon after cancer cell attached on endothelial cells. It was also found that the increase of intracellular calcium level in the endothelial cell was generated in the several decades second interval. These findings suggested that the increase of intracellular calcium should play an important role in the endothelial cell retraction. We also examine the signal transduction during the invasion in the cancer cell side. We found that increased expression of Rho, which is one of the low molecular weight GTP binding protein, enhanced cancer cell invasion.
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