Abstract 5177: Molecular targeting of αvβ3 integrin by echistatin inhibits tumor progression and metastasis in osteosarcoma

Abstract

Abstract Expression of αvβ3 integrin is associated with tumor progression and metastasis in several types of cancer, including metastatic osteosarcoma. We tested echistatin, an antagonist of αvβ3 integrin, as a molecular targeting drug, in an imageable orthotopic mouse model of human metastatic osteosarcoma. αvβ3 integrin expression was measured in a series of human osteosarcoma cell lines (143B parental and LM1-LM4) with increasing metastatic potential, using RT-PCR and immunoprecipitation. The cell lines expressed GFP in the nucleus and RFP in the cytoplasm and therefore could be imaged down to the subcellular level in vitro and in vivo. αvβ3 integrin expression correlated with the metastatic potential of the cells, with the LM4 cells showing the highest expression and highest metastatic capability, 6-fold and 18-fold, respectively, compared to parental 143B cells. In vitro cell proliferation of LM4 was inhibited by echistatin (p<0.01). In vitro migration, invasion, and adhesion of LM4 were also inhibited by echistatin (p<0.01). Tumor-induced angiogenesis by LM4 in the chick CAM model was also inhibited by echistatin (p<0.05). Mice treated with an echistatin-doxorubicin conjugate had significantly smaller primary tumors and longer survival compared to control untreated tumor-bearing mice (p<0.05 and p<0.01, respectively). Treatment with echistatin resulted in decreased experimental pulmonary metastases, imaged at the cellular level, in a nude mouse model compared to the untreated control (p<0.01). The results of this study indicate that αvβ3 integrin plays an essential role in osteosarcoma metastasis and that echistatin has potential to target αvβ3 integrin and inhibit tumor progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5177. doi:1538-7445.AM2012-5177