Decorin-Induced Growth Inhibition Is Overcome through Protracted Expression and Activation of Epidermal Growth Factor Receptors in Osteosarcoma Cells

Abstract

Decorin is an established natural oncosuppressive factor whose action is being studied in detail. Recently, decorin gene therapy formulations using adenoviral vectors have been shown in several animal models with very promising results. The present study describes the first exception to the established oncosuppression model using human osteosarcoma cells. MG-63 osteosarcoma cells were found to constitutively produce decorin, and furthermore, to be resistant to decorin-induced growth arrest. On the contrary, decorin seemed to be beneficial to osteosarcoma cells because it was necessary for MG-63 cell migration and acted as a mediator, counteracting the transforming growth factor-B2 -induced cytostatic function. Efforts to determine how MG-63 cells could overcome the decorin-induced cytostatic effect established that decorin in MG-63 cells does not induce p21 expression nor does it cause protracted retraction and inactivation of the epidermal growth factor receptor. Conversely, epidermal growth factor receptor seemed to be overexpressed and continuously phosphorylated. In view of the proposed design of decorin-based anticancer therapeutic strategies, our study provides new data on pathways that cancer cells might employ to overcome the established decorin-induced growth suppression. (Mol Cancer Res 2008;6(5):785 -94)

The Biology of Small Leucine-rich Proteoglycans in Bone Pathophysiology

“…Collectively, these findings strongly correlate with the well established antitumor properties of decorin (88). Interestingly, the only exception to the established oncosuppression model is the case of the highly aggressive MG-63 human osteosarcoma cells, found to constitutively produce decorin and to be resistant to decorin-induced growth arrest (89).…”

TLR5 involvement in attenuated IL-8 production in nuclear decorin silenced oral mucosal dysplastic keratinocytes and squamous cell carcinoma

“…Decorin is normally present in the extracellular stromal compartment and analyses of various tumors indicate that it is rarely expressed by cancer cells. However, studies by us and others indicate that there are exceptions to this prevailing decorin expression and decorin mediated cancer growth and suppression model [21,26,27]. Ectopic decorin expression has been linked to increased vascular endothelial growth factor expression and increased angiogenesis [28].…”

Decorin-Mediated Effects in Cancer Cell Biology

“…Schematic representation of the major pathways that are employed for the decorin-mediated effects on PDGF-BB [31], TGFb [32], and EGF [33] functions. a recent study significant differences were identified between the decorin expression profiles of normal osteoblastic cells and osteosarcoma cells [26]. When analyzing the biological significance of this finding, new data emerged [26] which deviated from the established decorin-induced cytostatic pathway.…”