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


CONCLUSIONS
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.
Oh
Jeong-Hyun
JH
Department of Biological Sciences, School of Medicine, Ajou University, Suwon 443-749, South Korea.
Kim
Ji-Hye
JH
Ahn
Hak-Jun
HJ
Yoon
Jong-Hyuck
JH
Yoo
Seung-Chul
SC
Choi
Dong-Soon
DS
Lee
In-Seon
IS
Ryu
Hee-Sug
HS
Min
Churl K
CK
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D019030:Receptors, Vitronectin / Q000378:metabolism; D053668:Syndecan-1 / Q000096:biosynthesis*; D015533:Transcriptional Activation
D016328:NF-kappa B; D019030:Receptors, Vitronectin; C508241:SDC1 protein, human; D053668:Syndecan-1; C064660:integrin alphaVbeta5; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020780:Matrix Metalloproteinase 9