Abstract 1817: Resistin induces angiogenesis and lymphangiogenesis in human chondrosarcoma

Abstract

Chondrosarcoma is a common kind of bone cancers, and it may develop distant metastasis, followed by a significant decline in overall survival. However, there are still no specific therapeutic methods for it today. For tumors to metastasis, angiogenesis and lymphangiogenesis are both important in the early processes. Therefore, inhibiting the development of angiogenesis and lymphangiogenesis could be a method to decline tumor metastasis. Resistin was discovered as an adipocyte-secreting adipokine, which may play a critical role in modulating cancer pathogenesis. In our lab, we previously found that resistin appears to increase MMP-2 expression and then promotes metastasis in human chondrosarcoma cells. Nevertheless, the role of resistin in angiogenesis and lymphangiogenesis of human chondrosarcoma is still unknown. To examine angiogenetic and lymphangiogenetic effects of resistin, we used human endothelial progenitor cells (EPCs) and lymphatic endothelial cells (LECs) to mimic capillary and lymphatic vessels formation. The results indicated that resistin-treated chondrosarcoma cell lines promoted EPCs VEGF-A-dependent as well as LECs VEGF-C-dependent tube formation and cell migration. Then we confirmed that treating cells with resistin increased VEGF-A and VEGF-C expression in human chondrosarcoma cell lines. Moreover, we found resistin-induced VEGF-A and VEGF-C expressions are mediated by PI3K/AKT signaling and by the activation of c-Src separately. In addition, resistin decreased the expression of miR-16-5p via PI3K/AKT pathway, and so of miR-186 via c-Src. We also demonstrated that miR-186 directly targeted on VEGF-C 3’ untranslated region, and regulated the VEGF-C production. Besides, we found the expressions of resistin, VEGF-A and VEGF-C was higher in human chondrosarcoma biopsy tissues than those in normal cartilage. Taken together, resistin not only promotes human chondrosarcoma angiogenesis through the activation of PI3K/AKT signaling pathway and down-regulating miR-16-5p expression, but also promotes human chondrosarcoma lymphangiogenesis through the activation of c-Src and down-regulating miR-186. Consequently, resistin may represent a potential novel molecular therapeutic target for human chondrosarcoma therapeutic treatment. Citation Format: Meng-Ju Chi, Chih-Yang Lin, Chih-Hsin Tang. Resistin induces angiogenesis and lymphangiogenesis in human chondrosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1817. doi:10.1158/1538-7445.AM2017-1817