Decorin-mediated effects in cancer cell biology.
Decorin is a multifunctional molecule of the extracellular matrix. Among the multitude of assigned functions the most intriguing is the ability to inhibit the growth and the metastasis of a wide range of cancer cells in vitro. Decorin was established to directly interact with EGFR and erb2, inducing protracted receptor internalization, which results in attenuation of the receptor-mediated intacellular signaling and induction of apoptosis. Studies by our group of osteosarcoma cells described the first exception to the established decorin-mediated growth suppression model. Osteosarcoma cells constitutively produced decorin and they were not sensitive to decorin-induced growth arrest. On the contrary, decorin seemed to be beneficial to osteosarcoma cells, since it was necessary for cell migration and acted as mediator, counteracting the TGFbeta2-induced cytostatic function. Importantly, decorin did not induce p21 expression whereas EGFR appeared to be overexpressed and continuously phosphorylated in our osteosarcoma model. These data provide new insight on pathways that cancer cells might employ to overcome the established decorin-induced growth suppression.
Zafiropoulos
Alexandros
A
Medical School, University of Crete, Heraklion, Greece.
Tzanakakis
George N
GN
D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D058575:Decorin; D066246:ErbB Receptors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011509:Proteoglycans; D066246:ErbB Receptors