부산대학교 도서관

Chondrosarcoma is a malignant bone tumor characterized by the production of a modified cartilage-type extracellular matrix (ECM). In the present study, the expression levels of the small leucine-rich proteoglycans (SLRPs), decorin, biglycan and lumican, were examined in the HTB94 human chondrosarcoma cell line. HTB94 cells were found to express and secrete the 3 SLRP members. RT-qPCR and western blot analysis demonstrated that lumican was the most abundantly secreted SLRP, whereas decorin and biglycan expression levels were low. The utilization of short interfering RNA specific for the decorin, biglycan, and lumican genes resulted in the efficient downregulation of the respective mRNA levels (P[less than or equal to]0.001). The growth of the HTB94 cells was stimulated by lumican (P[less than or equal to]0.001), whereas their migration and adhesion were not affected (P=NS). By contrast, these cellular functions were not sensitive to a decrease in low endogenous levels of decorin and biglycan. Lumicandeficiency significantly inhibited both basal and insulin-like growth factor I (IGF-I)-induced HTB94 cell growth (P[less than or equal to]0.001 and P[less than or equal to]0.01, respectively). These effects were executed through the insulin-like growth factor I receptor (IGF-IR), whose activation was markedly attenuated (P[less than or equal to]0.01) in lumican-deficient HTB94 cells. The downregulation of lumican induced the substantial inhibition of extracellular regulated kinase (ERK1/2) activation (P[less than or equal to] 0.01), indicating that ERK1/2 is a necessary component of lumican/IGF-IR-mediated HTB94 cell proliferation. Moreover, the lumican-deficient cells exhibit increased mRNA levels of p53 (P[less than or equal to]0.05), suggesting that lumican facilitates HTB94 cell growth through an IGF-IR/ERK1/2/p53 signaling cascade. On the whole, the findings of the present study demonstrate that endogenous lumican is a novel regulator of HTB94 cell growth. Key words: chondrosarcoma, lumican, small leucine-rich proteoglycans, cell growth, insulin-like growth factor receptor I, extracellular regulated kinase 1/2
Introduction Chondrosarcoma is a malignant bone tumor characterized by the production of a modified cartilage-type extracellular matrix (ECM). It is a heterogeneous, mesenchymal origin tumor that exhibits different histopathology and [...]