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Syndecan-1 enhances the endometrial cancer invasion by modulating matrix metalloproteinase-9 expression through nuclear factor kappaB.

Authors
Oh, JH; Kim, JH; Ahn, HJ; Yoon, JH; Yoo, SC; Choi, DS; Lee, IS; Ryu, HS; Min, CK
Citation
Gynecologic oncology, 114(3):509-515, 2009
Journal Title
Gynecologic oncology
ISSN
0090-82581095-6859
Abstract
OBJECTIVES: Up-regulated expression of syndecan-1, a member of the transmembranous proteoglycans that serves as a co-receptor for a wide pool of extracellular ligands, has been ascribed to the promotion of growth of various cancers including breast, ovarian, and endometrial cancers. Here, we have extended these observations to gain insight into correlation between the expression level of syndecan-1 and its tumor-promoting characteristics, particularly, cancer invasion, in endometrial cancer.



METHODS: Human syndecan-1 was stably transfected into three human endometrial cancer cell lines, and its effects were examined with respect to cell survival/proliferation and invasion. In addition, the activation of underlying signaling components, including integrins, focal adhesion kinase (FAK), and nuclear factor kappaB (NF-kappaB) was examined. The activity of NF-kappaB as a transcription factor for matrix metalloproteinase (MMP)-9 was assessed.



RESULTS: The innate expression level of syndecan-1 was moderate to high in all endometrial cancer cell lines. Overexpression of syndecan-1 promoted tumor cell proliferation concomitant with the activation of NF-kappaB. Furthermore, overexpression of syndecan-1 markedly enhanced the cancer invasion accompanied by enhanced expression of integrin alphav/beta5 and enhanced phosphorylation of FAK. The transcriptional activation of MMP-9 by NF-kappaB was up-regulated in syndecan-1 overexpression.



CONCLUSION: These findings provide evidence that supports that syndecan-1 may have a critical role in carcinogenic progression, particularly, contributing to the development of proliferative and invasive phenotype through NF-kappaB-mediated MMP-9 gene expression in endometrial cancer.
MeSH terms
Adenocarcinoma/geneticsAdenocarcinoma/metabolism*Adenocarcinoma/pathologyCell Growth Processes/physiologyCell Line, TumorCell Survival/physiologyEndometrial Neoplasms/geneticsEndometrial Neoplasms/metabolism*Endometrial Neoplasms/pathologyFemaleFocal Adhesion Protein-Tyrosine Kinases/metabolismHumansMatrix Metalloproteinase 9/biosynthesis*Matrix Metalloproteinase 9/geneticsNF-kappa B/geneticsNF-kappa B/metabolism*Neoplasm InvasivenessPhosphorylationReceptors, Vitronectin/metabolismSyndecan-1/biosynthesis*Transcriptional Activation
DOI
10.1016/j.ygyno.2009.05.027
PMID
19539355
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Obstetrics & Gynecology
AJOU Authors
윤, 종혁유, 승철유, 희석
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