Overexpressed Decorin in Pancreatic Cancer

Abstract

Purpose: The aim of this study was to investigate the expression and significance of decorin in pancreatic cancer.Experimental Results: Pancreatic cancer was characterized by striking overexpression of decorin mRNA in tumor tissues (9-fold by real-time quantitative PCR; 44 patients versus 18 healthy donors; P < 0.01). Strong decorin immunostaining was observed in the extracellular matrix of pancreatic cancer tissue, whereas tumor cells were devoid of decorin. Double staining for anti-smooth muscle actin and decorin and reverse transcription-PCR analysis of primary cultures revealed pancreatic stellate cells as the putative source of decorin. Human recombinant decorin was able to suppress growth of pancreatic cancer cells in vitro through p21-mediated G 1 -S block of the cell cycle. However, in contrast to the previously described chemotherapy-potentiating capacity of decorin, this proteoglycan attenuated the cytostatic action of carboplatin and gemcitabine toward pancreatic cancer cells.Conclusions: Decorin might exert an antiproliferative effect toward pancreatic cancer cells, thus playing a role in a host stromal reaction aimed at sequestering and inhibiting growing malignant cells. However, in clinical settings, the importance of collagen-associated decorin as a moderate antitumor modality would be undermined by its ability to attenuate the efficiency of chemotherapeutics. Considering the general failure of adjuvant therapies in pancreatic cancer, the role of decorin in this process warrants further investigation.

Methylated +58CpG site decreases DCN mRNA expression and enhances TGF-β/Smad signaling in NSCLC cells with high metastatic potential

“…Compelling evidence has shown that DCN contributes to inhibition of tumor growth and metastasis (13,(15)(16)(17)(18)(19)34). Goldoni et al reported that DCN can display an anti-metastatic role in breast cancer (16).…”

“…DCN-mediated inhibition of colorectal cancer migration is associated with E-cadherin (13,(15)(16)(17)(18)(19)34). Here we examined expression of E-cadherin in 95D expressing low DCN and 95C expressing high DCN, and found that E-cadherin expression was significantly lower in 95D cells (0.25±0.05) than 95C cells (0.73±0.07) (P=0.016) (Fig.…”

Alteration of Tumor Microenvironment for Improved Delivery and Intratumor Distribution of Nanocarriers

“…53) decorin plays a role as an important determinant of macromolecule diffusion in tumor tissue Ecm. decorin digestion may produce a widening of collagen interfibrillar spaces.…”

Characterization of mouse embryonic stem cell differentiation into the pancreatic lineage in vitro by transcriptional profiling, quantitative RT-PCR and immunocytochemistry

“…Schonherr (2001) and Koninger et al (2004). Serpine2 transcripts were slightly up-regulated in committed progenitor cells, whereas significant levels were detected in adult pancreas.…”

“…Decorin (Dcn) belongs to the group of small leucine-rich proteoglycans expressed by sprouting endothelial cells. Decorin plays a role in regulating collagen fibril formation and stabilization, and modulates cell adhesion as well as transforming growth factor-β activity [for review see (Koninger et al, 2004;Kresse and Schonherr, 2001)]. Dcn transcripts were upregulated in committed progenitor cells, but not in liver and pancreas.…”