Abstract
Although elevated syndecan-2 expression is known to be crucial for the tumorigenic activity in colon carcinoma cells, how syndecan-2 regulates colon cancer is unclear. In human colon adenocarcinoma tissue samples, we found that both mRNA and protein expression of syndecan-2 were increased, compared with the neighboring normal epithelium, suggesting that syndecan-2 plays functional roles in human colon cancer cells. Consistent with this notion, syndecan-2-overexpressing HT-29 colon adenocarcinoma cells showed enhanced migration/invasion, anchorage-independent growth, and primary tumor formation in nude mice, paralleling their morphological changes into highly tumorigenic cells. In addition, our experiments revealed that syndecan-2 enhanced both expression and secretion of matrix metalloproteinase-7 (MMP-7), directly interacted with pro-MMP-7, and potentiated the enzymatic activity of pro-MMP-7 by activating its processing into the active MMP-7. Collectively, these data strongly suggest that syndecan-2 functions as a docking receptor for pro-MMP-7 in colon cancer cells.
Highlights
The characteristics and functions of cancer cells are critically influenced by the actions of cell adhesion receptors, which mediate interactions of cancer cells with the extracellular matrix (ECM)3 and the cytoskeleton [1]
Genome-scale microarray analysis showed that syndecan-2 overexpression in HT-29 cells significantly increased the expression level of matrix metalloproteinases (MMPs)-7, but not that of MMP-2 or MMP-9, which are centrally involved in tumor invasion and metastasis (Fig. 4)
Our previous study showed that increased syndecan-2 decreased expression of matrix metalloproteinase-7 (MMP-7) led to reductions in the syndeexpression led to enhanced cell proliferation and migration/inva- can-2-mediated enhancement of cell migration (Fig. 5)
Summary
The characteristics and functions of cancer cells are critically influenced by the actions of cell adhesion receptors, which mediate interactions of cancer cells with the extracellular matrix (ECM) and the cytoskeleton [1]. At different points during carcinogenesis, the cell adhesion receptors regulate various cancer cell functions, including cell growth, differentiation, cell survival, angiogenesis, and inflammation [2, 3]. In other studies, syndecan-1 expression is reportedly up-regulated in prostate, lung, and breast cancers [13,14,15]. Recent studies have shown that MMP-7 interacts with the specific molecular genetic and signaling pathways involved in colorectal cancer development. Studies have shown that the cell surface localization of MMPs, which is tightly regulated in normal cells, is very important for carcinogenesis-related processing. The formation of MMP1⁄7adhesion receptor complexes appears to be a common pathway through which soluble MMPs are localized to the cell surface
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