Increased expression of insulin-like growth factor-1 receptor is correlated with tumor metastasis and prognosis in patients with osteosarcoma.

The aim of this study was to investigate the association of insulin-like growth factor-1 receptor (IGF-1R) with metastasis and prognosis of osteosarcoma patients. RT-PCR and Western blot assays were performed to detect IGF-1R mRNA and protein expression in 26 osteosarcoma and noncancerous bone tissues. Immunohistochemistry was performed to analyze the correlation of IGF-1R expression in 84 osteosarcoma tissues with clinicopathological factors or survival of patients. Lentivirus-mediated RNA interference system was employed to downregulate IGF-1R expression and analyze the effects of IGF-1R downregulation on invasion and metastasis of osteosarcoma cells. The relative levels of IGF-1R mRNA and protein expression were significantly higher in osteosarcoma tissues than in corresponding noncancerous bone tissues. The expression of IGF-1R protein was closely associated with surgical stage and distant metastasis of osteosarcoma patients. Osteosarcoma patients with high IGF-1R expression had poorer survival, and multivariate Cox analyses showed that high IGF-1R expression was an independent prognostic maker. Lentivirus-mediated targeting IGF-1R could significantly inhibit adhesion, migration, invasion, and metastasis of osteosarcoma cells, which might be correlated with of inactivation of Akt signaling pathway. IGF-1R is an independent prognostic marker for osteosarcoma patients and increased expression of this molecular is correlated with metastasis of osteosarcoma.

Wang YH ，Han XD ，Qiu Y ，Xiong J ，Yu Y ，Wang B ，Zhu ZZ ，Qian BP ，Chen YX ，Wang SF ，Shi HF ，Sun X ... -  《-》

The novel synthesized 6-fluoro-(3-fluorophenyl)-4-(3-methoxyanilino)quinazoline (LJJ-10) compound exhibits anti-metastatic effects in human osteosarcoma U-2 OS cells through targeting insulin-like growth factor-I receptor.

Chen KT ，Hour MJ ，Tsai SC ，Chung JG ，Kuo SC ，Lu CC ，Chiu YJ ，Chuang YH ，Yang JS ... -  《-》

Clinicopathological significance of the gene expression of matrix metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2 and insulin-like growth factor-1 receptor in patients with colorectal cancer: insulin-like growth factor-1 re

Oshima T ，Akaike M ，Yoshihara K ，Shiozawa M ，Yamamoto N ，Sato T ，Yamada R ，Fujii S ，Rino Y ，Kunisaki C ，Tanaka K ，Masuda M ，Imada T ... -  《ONCOLOGY REPORTS》

Insulin-like growth factor (IGF) I down-regulates type 1 IGF receptor (IGF 1R) and reduces the IGF I response in A549 non-small-cell lung cancer and Saos-2/B-10 osteoblastic osteosarcoma cells.

Bostedt KT ，Schmid C ，Ghirlanda-Keller C ，Olie R ，Winterhalter KH ，Zapf J ... -  《EXPERIMENTAL CELL RESEARCH》

Clinical value of signal transducers and activators of transcription 3 (STAT3) gene expression in human osteosarcoma.

The dysregulation of signal transducers and activators of transcription 3 (STAT3) has been reported to be associated with tumor progression, angiogenesis and metastasis. The purpose of this study was to analyze the clinical value of STAT3 expression in human osteosarcoma. First, semi-quantitative RT-PCR was performed to detect the expression of STAT3 mRNA in normal bone tissues, chondroma tissues and osteosarcoma tissues. Then, immunohistochemistry was performed to detect the expression of STAT3 protein in 76 osteosarcoma tissues and the relationship of STAT3 protein expression with clinicopathologic factors or prognosis of osteosarcoma patients. RNA interference (RNAi) technology was employed to inhibit STAT3 expression. MTT and flow cytometric assays were performed to analyze the effect of STAT3 inhibition on proliferation and apoptosis of osteosarcoma cells. Finally, the expression of STAT3-related target genes were also determined. Results showed that osteosarcoma tissues showed significantly higher expression levels of STAT3 mRNA than normal bone or chondroma tissues (P<0.05). Immunohistochemistry showed that the staining of STAT3 protein was mainly located in cytoplasm of osteosarcoma cells in osteosarcoma tissue samples. The high level of STAT3 protein was associated with poor tumor differentiation and presentation of metastasis (P=0.039 and 0.022). Moreover, the 5-year overall and relapse-free survival rates for osteosarcoma patients with high STAT3 expression were lower than those for patients with low STAT3 expression. In addition, the status of STAT3 protein expression was an independent prognostic factor for both disease-free survival (P=0.0235) and overall survival (P=0.0032). RNAi-mediated STAT3 inhibition could induce proliferation inhibition and apoptosis enhancement in osteosarcoma cells, which might be associated with inhibition of some anti-apoptosis genes. Overall, STAT3 plays crucial roles in osteosarcoma development and might become a potential molecular target for gene therapy of human osteosarcomas.

Wang YC ，Zheng LH ，Ma BA ，Zhou Y ，Zhang MH ，Zhang DZ ，Fan QY ... -  《-》