Abstract

The small extracellular matrix proteoglycan decorin which possesses a potent antitumor activity has been shown to be present in various amounts in the stroma of several tumors including those of the breast. Regarding decorin in breast malignancies the published data are conflicting, i.e., whether breast cancer cells express it or not. Here, we first compared decorin gene expression levels between healthy human breast tissue and selected types of human breast cancer using GeneSapiens databank. Next, we localized decorin mRNA in tissue specimen of normal human breast, intraductal breast papillomas and various histologic types of human breast cancer using in situ hybridization (ISH) with digoxigenin-labeled RNA probes for decorin. We also examined the effect of decorin transduction on the behavior of cultured human breast cancer MCF7 cells. Analysis of GeneSapiens databank revealed that in various human breast cancers decorin expression is significant. However, ISH results clearly demonstrated that human breast cancer cells independently of the type of the cancer do not express decorin mRNA. This was also true for papilloma-forming cells of the human breast. Indeed, decorin gene expression in healthy human breast tissue as well as in benign and malignant tumors of human breast was shown to take place solely in cells of the original stroma. Decorin transduction using decorin adenoviral vector in decorin-negative MCF7 cells resulted in a significant decrease in the proliferation of these cells and changed cell cohesion. Decorin-transduced MCF7 cells also exhibited increased apoptosis. In conclusion, our study shows that in human breast tissue only cells of the original stroma are capable of decorin gene expression. Our study also shows that transduction of decorin in decorin-negative human breast cancer cells markedly modulates the growth pattern of these cells.

Highlights

  • In recent years, growing interest has been focused on the role and therapeutic potential of extracellular matrix (ECM) macromolecules in various diseases including the evolution and progression of cancer (Hielscher et al 2012; Jarvelainen et al 2009; Lu et al 2012; Marastoni et al 2008)

  • In order to analyze published data on decorin gene expression in different types of human breast cancer, we used an in silico database from the GeneSapiens website (Kilpinen et al 2008)

  • The analysis indicated that the relative decorin gene expression is significant in both healthy and various malignant conditions of human breast tissue (Fig. 1)

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Summary

Introduction

In recent years, growing interest has been focused on the role and therapeutic potential of extracellular matrix (ECM) macromolecules in various diseases including the evolution and progression of cancer (Hielscher et al 2012; Jarvelainen et al 2009; Lu et al 2012; Marastoni et al 2008). This is because today we understand that ECM macromolecules form an inert, space-filling. A lot of interest has been paid to the potential use of decorin as an anticancer agent in the future (Neill et al 2012; Pucci-Minafra et al 2008; Theocharis et al 2010)

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