Significance of stromal decorin expression during the progression of breast cancer

Abstract

Abstract. Decorin, a small leucine-rich proteoglycan and important component of the extracellular matrix (ECM), is a natural anticancer agent that modulates several receptors involved in cell growth and survival. Reductions in decorin expression may weaken the ECM and enhance the effectiveness of these receptors and may, consequently, lead to tumor spreading. To determine the contribution of stromal decorin regulation in the development of breast cancer and in tumor invasiveness, immunohistochemistry was used to examine the expression of stromal decorin in 120 breast cancer tissue samples. In patients with invasive breast carcinoma (IBC), stromal decorin expression was highest in normal gland tissue, lower in in situ components and the lowest in invasive components. Stromal decorin expression adjacent to malignant cells in IBC tumors was also significantly weaker compared to that in pure ductal carcinoma in situ (DCIS). These findings indicate that there is a striking difference in the stromal decorin expression around normal glands and around DCIS or IBC tumors. Reduced levels of decorin were associated with more aggressive disease; this finding was consistent with the view that reduced decorin expression may facilitate tumorigenesis, tumor invasion and/or tumor growth. Given these and other reported findings, evaluating stromal decorin expression may be useful in assessing prognosis and malignant potential; therefore, a large-scale study of decorin expression is warranted. IntroductionThe extracellular matrix (ECM), which provides structural support to cells, is the extracellular material in tissue that generally has a role in the regulation of cell proliferation, differentiation and wound healing. Components of the ECM are now being recognized as key signaling molecules that affect the invasion and metastasis of cancer. It has become evident that the ECM modulates cellular proliferation and differentiation by affecting not only growth factors, but also various receptors involved in controlling morphogenesis and cell growth (1). Decorin is a component of the ECM that is synthesized primarily by fibroblasts and myofibroblasts (2) and that regulates collagen fibrillogenesis (3,4). Based on in vitro assays, decorin is a potent inhibitor of tumor cell proliferation as it interacts with transforming growth factor-β (TGF-β) (5) and affects several receptors, epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGF-IR) and lowdensity lipoprotein receptor-related protein (LRP) (2). Evidence from in vitro experiments indicates that decorin is a potent inhibitor of tumor cell proliferation, therefore, the antitumor effects of decorin have been tested in vivo. A cytomegaloviral vector containing the decorin transgene has been shown to inhibit tumorigenesis and metastatic spreading of breast carcinoma (6). A recombinant protein that comprises only the core of the human decorin protein inhibits metastatic spreading to the lung in xenograft models of breast carcinoma (7).The natural history of breas...

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder

“…On the contrary to the report published by El Behi et al 41 that states overexpression of Decorin in muscle invasive bladder cancer, we observed a reduced protein expression of Decorin by IHC and western blotting in tumour tissue as compared with adjacent non-tumour tissue. Previously, Sainio et al 42 had shown a similar low stromal Decorin expression in areas rich in bladder cancer cells as compared with non-malignant bladder tissue, and Oda et al 43 had observed a reduced immunostaining in stroma of invasive cancer and in situ breast cancer as compared with normal breast tissue. Thus, our findings in bladder cancer for the expression of Decorin are in accordance with the previous studies done in prostate, breast, and oesophageal cancers.…”

The extracellular matrix in breast cancer predicts prognosis through composition, splicing, and crosslinking

“…15 BC lumican was highly abundant relative to decorin, while biglycan and fibromodulin are only detected occasionally [143] lumican mRNA was increased in tumors while decorin mRNA was decreased in neoplastic relative to adjacent normal stroma along with an increase in lumican, but not decorin IHC for decorin 98 samples IBC and 22 were from patients with DCIS Decorin was observed in stroma but not epithelia. Average decorin expression decreased from normal to DCIS to IDC [48] IHC for Syndecan 1,4, and Glypican 1 207 BC Glypican-1 detected in a small sample of BC [144] Higher level of Syndecan 1 and -4 predicted higher…”

“…Importantly, gene expression patterns of normal stroma adjacent to breast cancers shows a different gene expression pattern from normal tissue from unaffected patients [46]. Changes in stromal ECM are observed even in ductal carcinoma in situ (DCIS), where carcinoma cells are confined within an intact basement membrane, including increased deposition of versican [47], loss of decorin [48], and altered expression of Col11A1 [46,49].…”

Matricellular proteins as regulators of cancer metastasis to bone

“…Decorin is also found in tumor ECM and is mainly attributed to surrounding, non-malignant stromal cells (tumor cells express little decorin) [15–17]. However, decorin expression is decreased in stromal cells of many tumors compared to normal tissues and inversely correlates with prognosis of breast and lung carcinomas [16, 18, 19]. Declined decorin in the bone marrow matrix is also associated with the clinical progression of multiple myeloma [20].…”

“…Declined decorin in the bone marrow matrix is also associated with the clinical progression of multiple myeloma [20]. Interestingly, decorin acts as a tumor suppressor in a number of cancers, including breast, prostate, ovarian and colon [16, 21–23]. This function is partially due to the ability of decorin to bind to and inhibit function of RTKs such as epidermal growth factor receptor (EGFR), insulin-like growth factor receptor I (IGF-IR) and hepatocyte growth factor receptor (c-Met) [24–26].…”