Syndecan-1 overexpression promotes tumor growth and angiogenesis in an endometrial cancer xenograft model.
OBJECTIVE
Upregulation of syndecan-1, a member of the transmembranous proteoglycans that serves as a coreceptor for a wide pool of extracellular ligands, has been well documented in enabling the promotion of growth and invasion of endometrial cancer. As a step toward understanding a potential role for syndecan-1 in this process, we questioned whether syndecan-1 upregulates tumor-promoting characteristics, particularly, angiogenesis in an in vivo human xenograft tumor model.


METHODS
Human syndecan-1 was stably transfected into human endometrial adenocarcinoma 1A cells, and resulting transfectants were subcutaneously grafted into athymic mice; their outcomes were examined with respect to the enhancement of tumor growth and angiogenesis by immunohistochemistry, immunoblotting, and zymography.


RESULTS
Overexpression of syndecan-1 promoted tumor growth concomitant with increased angiogenesis in tumor xenografts as evidenced by an increase in immunoreactivity for vascular endothelial growth factor and vascular endothelial cell marker CD34. Furthermore, zymographic studies revealed that syndecan-1 overexpression markedly enhanced activities of matrix metalloproteinases 2 and 9.


CONCLUSIONS
This is the first in vivo xenograft analysis providing evidence that supports that syndecan-1 has a critical role in carcinogenic progression, particularly, contributing to the development of angiogenesis and invasive phenotype in association with matrix metalloproteinases 2 and 9 activations in endometrial cancer.
Department of Biological Sciences, Ajou University, Suwon, South Korea.
Jeong-Hyun
JH
Oh
Hae-Sun
HS
Lee
Sang-Hyun
SH
Park
Hee-Sug
HS
Ryu
Churl K
CK
Min
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D053668:Syndecan-1 / Q000096:biosynthesis*; D014183:Transplantation, Heterologous; D015854:Up-Regulation
D053668:Syndecan-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9