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

Department of Orthopaedic Surgery, The Affiliated Drum Tower Hospital of Nanjing, University Medical School, Nanjing, Jaingsu, P.R. China.
Journal of Surgical Oncology (Impact Factor: 3.24). 03/2012; 105(3):235-43. DOI: 10.1002/jso.22077
Source: PubMed


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.

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    • "In addition, a recent study indicated that IGF-1R was involved in the in vitro behavior of metastatic OS cell lines (75). A subsequent study found that the expression of the IGF-1R protein was closely associated with the surgical stage and distant metastasis of OS patients, and that IGF-1R can be used as an independent prognostic marker for OS patients (76). "
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    ABSTRACT: Due to the emergence of adjuvant and neoadjuvant chemotherapy, the survival rate has been greatly improved in osteosarcoma (OS) patients with localized disease. However, this survival rate has remained unchanged over the past 30 years, and the long-term survival rate for OS patients with metastatic or recurrent disease remains poor. To a certain extent, the reason behind this may be ascribed to the chemoresistance to anti-OS therapy. Chemoresistance in OS appears to be mediated by numerous mechanisms, which include decreased intracellular drug accumulation, drug inactivation, enhanced DNA repair, perturbations in signal transduction pathways, apoptosis- and autophagy-related chemoresistance, microRNA (miRNA) dysregulation and cancer stem cell (CSC)-mediated drug resistance. In addition, methods employed to circumvent these resistance mechanism have been shown to be effective in the treatment of OS. However, almost all the current studies on the mechanisms of chemoresistance in OS are in their infancy. Further studies are required to focus on the following aspects: i) Improving the delivery of efficacy through novel delivery patterns; ii) improving the understanding of the signal transduction pathways that regulate the proliferation and growth of OS cells; iii) elucidating the signaling pathways of autophagy and its association with apoptosis in OS cells; iv) utilizing high-throughput miRNA expression analysis to identify miRNAs associated with chemoresistance in OS; and v) identifying the role that CSCs play in tumor metastasis and in-depth study of the mechanism of chemoresistance in the CSCs of OS.
    Oncology letters 05/2014; 7(5):1352-1362. DOI:10.3892/ol.2014.1935 · 1.55 Impact Factor
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    • "Osteosarcoma is the most common bone cancer in children (Mirabello et al., 2009). Osteosarcoma cell lines are dependent on IGF-1 via IGF-1R for in vitro growth (Kappel et al., 1994), and IGF-1R expression has been associated with poor prognosis (Wang et al., 2012). Nearly 20 years after that first observation, a mouse xenograft model using six different osteosarcoma cell lines demonstrated objective responses to R1507, a monoclonal anti-IGF1R antibody, in vivo. "
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    ABSTRACT: Data from over 20 years ago demonstrated potential use for insulin-like growth factor (IGF) signaling modulators, specifically with IGF-1R antagonists, in a variety of pediatric and adolescent cancers, particularly in sarcomas. However, in spite of promising preclinical data, IGF-1R inhibitors have not had the success as single agents that was originally hoped for in clinical trials. Several potential mechanisms exist by which tumors are resistant to IGF-1R inhibitors. Notably, these resistance mechanisms are currently best understood in Ewing sarcoma and alveolar rhabdomyosarcoma. Various treatment schema have been proposed as a potential way to overcome this resistance. The use of IGF-1R inhibitors, mechanisms of resistance, and current ongoing clinical studies using IGF-1R inhibitors in pediatric cancers are reviewed here.
    Frontiers in Oncology 02/2013; 3:9. DOI:10.3389/fonc.2013.00009
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    • "Inhibition of IGF-IR with some monoclonal antibodies enhances the antitumor effects in several OS xenograft models [170, 171]. More recently, a clinical study has demonstrated that high IGF-IR expression is a poor prognostic factor for OS patients leading to OS development and metastasis [172]. Thus, IGF-IR targeting therapy can be a novel strategy for the treatment of OS associated with metastasis. "
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    ABSTRACT: Osteosarcoma is the most frequent malignant primary bone tumor characterized by a high potency to form lung metastases which is the main cause of death. Unfortunately, the conventional chemotherapy is not fully effective on osteosarcoma metastases. The progression of a primary tumor to metastasis requires multiple processes, which are neovascularization, proliferation, invasion, survival in the bloodstream, apoptosis resistance, arrest at a distant organ, and outgrowth in secondary sites. Consequently, recent studies have revealed new insights into the molecular mechanisms of metastasis development. The understanding of the mechanism of molecular alterations can provide the identification of novel therapeutic targets and/or prognostic markers for osteosarcoma treatment to improve the clinical outcome.
    Sarcoma 02/2012; 2012(6):523432. DOI:10.1155/2012/523432
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