scholarly journals ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

Oncogene ◽  
2010 ◽  
Vol 30 (12) ◽  
pp. 1413-1421 ◽  
Author(s):  
R Yagi ◽  
M Tanaka ◽  
K Sasaki ◽  
R Kamata ◽  
Y Nakanishi ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Gastric Carcinoma ◽  
Peritoneal Dissemination ◽  
Carcinoma Cells ◽  
Scirrhous Gastric Carcinoma ◽  
Adhesion And Invasion

A novel K-samII/FGF-R2 autophosphorylation inhibitor is therapeutically useful for scirrhous gastric carcinoma with K-samII amplification

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14070-14070
Author(s):  
M. Yashiro ◽  
K. Nakamura ◽  
T. Sawada ◽  
H. Kawajiri ◽  
T. Shimizu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Gastric Carcinoma ◽  
Cancer Cells ◽  
Peritoneal Dissemination ◽  
Growth Factor Receptor ◽  
Carcinoma Cells ◽  
Apoptosis Pathway ◽  
Scirrhous Gastric Cancer ◽  
Scirrhous Gastric Carcinoma

14070 Background: Scirrhous gastric carcinoma, a diffusely infiltrating also known as linitis plastica-type carcinoma, carries the highest mortality of all gastric cancers. Scirrhous carcinoma cells with amplification of the activated K-samII gene, which encodes fibroblast growth factor receptor type 2 (FGF-R2), have a growth advantage during tumor progression The poor prognosis carried by scirrhous gastric cancer is closely associated with amplification of the K-samII/FGF-R2, a tyrosine kinase growth factor receptor. Ki23057, a newly developed small molecule acting K-samII/FGF-R2 inhibitor, is a kinase inhibitor that competes with ATP for the binding site in the kinase, thus strongly blocking phosphorylation of FGF-R2. The aim of the current study is to clarify the possibility of molecular target therapy with Ki23057 for treating scirrhous gastric cancer. Methods: Five human gastric cancer cell lines were used. OCUM-2MD3 and OCUM-8 were derived from scirrhous carcinomas. MKN-7, MKN-45 and MKN-74 cells were derived from non-scirrhous carcinomas. In vitro effects of Ki23057 on cell growth were determined by calculating the number of cancer cells. The influences of Ki23057 on the MAP kinase and PI3 kinase signaling pathways and the apoptosis pathway in the gastric cancer cells were also examined. For in vivo experiments, the Ki23057 was administered orally to mouse models of peritoneal dissemination. Results: K-samII amplification was found in OCUM-2MD3 and OCUM-8 cells, but not in MKN-7, MKN-45, or MKN-74 cells. Ki23057 significantly inhibited the proliferation of scirrhous cancer cells, but not non- scirrhous gastric carcinoma cells. Ki23057 decreased phosphorylation of K-samII/FGF-R2, ERK and Akt, and increased apoptosis in scirrhous cancer lines. The oral Ki23057 administration significantly (p<0.001) prolonged survival of mice with peritoneal dissemination following injection of OCUM-2MD3 scirrhous cancer cells. Conclusions: A novel K-samII/FGF-R2 phosphorylation inhibitor, Ki23057, appears therapeutically promising in scirrhous gastric carcinoma with K-samII amplification. No significant financial relationships to disclose.

scholarly journals TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in Ras/ERKs (extracellular-signal-regulated kinases) cascade activity dependent on c-Src activity

2004 ◽  
Vol 379 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hwang-Phill KIM ◽  
Mi-Sook LEE ◽  
Jiyon YU ◽  
Jin-Ah PARK ◽  
Hyun-Soon JONG ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Gastric Carcinoma ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Carcinoma Cells ◽  
Matrix Proteins ◽  
Src Family Kinase ◽  
Extracellular Signal ◽  
Activity Dependent ◽  
Tgf Β1

Signalling by integrin-mediated cell anchorage to extracellular matrix proteins is co-operative with other receptor-mediated signalling pathways to regulate cell adhesion, spreading, proliferation, survival, migration, differentiation and gene expression. It was observed that an anchorage-independent gastric carcinoma cell line (SNU16) became adherent on TGF-β1 (transforming growth factor β1) treatment. To understand how a signal cross-talk between integrin and TGF-β1 pathways forms the basis for TGF-β1 effects, cell adhesion and signalling activities were studied using an adherent subline (SNU16Ad, an adherent variant cell line derived from SNU16) derived from the SNU16 cells. SNU16 and SNU16Ad cells, but not integrin α5-expressing SNU16 cells, showed an increase in adhesion on extracellular matrix proteins after TGF-β1 treatment. This increase was shown to be mediated by an integrin α3 subunit, which was up-regulated in adherent SNU16Ad cells and in TGF-β1-treated SNU16 cells, compared with the parental SNU16 cells. After TGF-β1 treatment of SNU16Ad cells on fibronectin, Tyr-416 phosphorylation of c-Src was increased, but Ras-GTP loading and ERK1/ERK2 (extracellular-signal-regulated kinases 1 and 2) activity were decreased, which showed a dependence on c-Src family kinase activity. Studies on adhesion and signalling activities using pharmacological inhibitors or by transient-transfection approaches showed that inhibition of ERK1/ERK2 activity increased TGF-β1-mediated cell adhesion slightly, but not the basal cell adhesion significantly, and that c-Src family kinase activity and decrease in Ras/ERKs cascade activity were required for the TGF-β1 effects. Altogether, the present study indicates that TGF-β1 treatment causes anchorage-independent gastric carcinoma cells to adhere by an increase in integrin α3 level and a c-Src family kinase activity-dependent decrease in Ras/ERKs cascade activity.

scholarly journals Stromal Fibroblasts Mediate Extracellular Matrix Remodeling and Invasion of Scirrhous Gastric Carcinoma Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85485 ◽  
Author(s):  
Hideki Yamaguchi ◽  
Nachi Yoshida ◽  
Miho Takanashi ◽  
Yuumi Ito ◽  
Kiyoko Fukami ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Gastric Carcinoma ◽  
Carcinoma Cells ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Stromal Fibroblasts ◽  
Scirrhous Gastric Carcinoma

scholarly journals Upregulation of cancer-associated myofibroblasts by TGF-β from scirrhous gastric carcinoma cells

2011 ◽  
Vol 105 (7) ◽  
pp. 996-1001 ◽  
Author(s):  
Y Fuyuhiro ◽  
M Yashiro ◽  
S Noda ◽  
S Kashiwagi ◽  
J Matsuoka ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Carcinoma Cells ◽  
Scirrhous Gastric Carcinoma

scholarly journals ICAM-2 Gene Therapy for Peritoneal Dissemination of Scirrhous Gastric Carcinoma

2004 ◽  
Vol 10 (14) ◽  
pp. 4885-4892 ◽  
Author(s):  
Hiroaki Tanaka ◽  
Masakazu Yashiro ◽  
Takeshi Sunami ◽  
Yoji Sakate ◽  
Kinshi Kosaka ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gastric Carcinoma ◽  
Peritoneal Dissemination ◽  
Scirrhous Gastric Carcinoma
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