Metastasis-suppressor KAI1/CD82 induces homotypic aggregation of human prostate cancer cells through Src-dependent pathway.
- Author:
Bokeun JEE
1
;
Kideok JIN
;
Jang Hee HAHN
;
Hyung Geun SONG
;
Hansoo LEE
Author Information
1. Vascular System Research Center Division of Life Sciences, College of Natural Sciences Kangwon National University, Chunchon 200-701, Korea. hslee@kangwon.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell adhesion;
metastasis suppressor pro-teins;
neoplasm metastasis;
prostatic neoplasms;
Src-family kinases
- MeSH:
Adenocarcinoma/*metabolism/pathology/*secondary;
Antigens, Surface;
Cell Adhesion/genetics;
Cell Aggregation/genetics;
Gene Expression Regulation;
Genes, Tumor Suppressor;
Genes, src;
Human;
Male;
Membrane Glycoproteins/genetics/*metabolism;
Prostatic Neoplasms/*metabolism/pathology/*secondary;
Signal Transduction/genetics;
Tumor Cells, Cultured;
src-Family Kinases/genetics/metabolism
- From:Experimental & Molecular Medicine
2003;35(1):30-37
- CountryRepublic of Korea
- Language:English
-
Abstract:
To investigate the functional role of KAI1/CD82, a metastasis suppressor for human prostate cancer, in the regulation of homotypic cell adhesion, we transfected KAI1 cDNA into DU 145 human prostate cancer cells and established stable transfectant clones with high KAI1/CD82 expression. The KAI1 transfectant cells exhibited significantly increased homotypic cell aggregation in comparison with the control transfectant cells. This aggregation of the KAI1 transfectants was further enhanced upon exposure to anti-CD82 antibody, suggesting that KAI1/CD82 may be involved in the intracellular signaling for the cell adhesion. Among several signal pathway inhibitors tested, PP1, an inhibitor of Src family kinases, significantly suppressed homotypic aggregation of the KAI1 transfectant cells. Ligation of KAI1/CD82 with anti-CD82 antibody increased endogenous Src kinase activity of the KAI1 transfectant cells. When different types of src expression constructs were retransfected into the KAI1-transfected DU 145 cells, kinase-negative mutant src transfectant cells exhibited much lower homotypic aggregation than the mock cells transfected with an empty vector. Moreover, homotypic aggregation of the mutant src transfectant cells was not enhanced by KAI1/CD82 ligation with anti- CD82 antibody. These results suggest that Src mediates the intracellular signaling pathway of KAI1/CD82 for the induction of homotypic adhesion of human prostate cancer cells.
