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Lumican expression is positively correlated with the differentiation and negatively with the growth of human osteosarcoma cells
Author(s) -
Nikitovic Dragana,
Berdiaki Aikaterini,
Zafiropoulos Alexandros,
Katonis Pavlos,
Tsatsakis Aristidis,
Karamanos Nikos K.,
Tzanakakis George N.
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2007.06205.x
Subject(s) - lumican , keratan sulfate , osteosarcoma , proteoglycan , smad , cell growth , cancer research , cell culture , microbiology and biotechnology , chemistry , biology , extracellular matrix , transforming growth factor , biochemistry , genetics , decorin
Osteosarcoma is the most common primary bone tumour associated with childhood and adolescence. The possible role of the small leucine‐rich proteoglycan, lumican, in the growth and metastasis of various cancer types has recently been investigated. In this study, the expression of lumican was examined in moderately differentiated (MG‐63) and well‐differentiated (Saos 2) human osteosarcoma cell lines of high and low metastatic capability, respectively. Real‐time PCR, western blotting with antibodies against the protein core and keratan sulfate, and specific enzymatic digestions were the methods employed. The two human osteosarcoma cell lines were found to express and secrete lumican partly substituted with keratan sulfate glycosaminoglycans. Importantly, the non‐metastatic, well‐differentiated Saos 2 cells produced lumican at rates that were up to sevenfold higher than those of highly metastatic MG‐63 cells. The utilization of short interfering RNA specific for the lumican gene resulted in efficient down‐regulation of its mRNA levels in both cell lines. The growth of Saos 2 cells was inhibited by lumican, whereas their migration and chemotactic response to fibronectin were found to be promoted. Lumican expression was negatively correlated with the basal level of Smad 2 activation in these cells, suggesting that lumican may affect the bioavailability of Smad 2 activators. By contrast, these cellular functions of highly aggressive MG‐63 cells were demonstrated not to be sensitive to a decrease in their low endogenous lumican levels. These results suggest that lumican expression may be positively correlated with the differentiation and negatively correlated with the progression of osteosarcoma.