Abstract
Abstract HGF-mediated c-MET signaling plays a critical key in the progression of multiple myeloma. That signaling is associated with cell proliferation, drug resistance and osteoblast. In addition dynamic interplay between MM cell and bone marrow stromal cell regulates that signaling activation. The expression level of HGF in bone marrow plasma of MM patients is higher when compared to case control. However, the role of HGF-mediated c-Met was obscure in the progression of MM. In this study, we elucidate the role of c-Met signaling in osteogenesis in MM using co-culture system. In our previous data, we found that the expression levels of HGF in bone marrow serum of multiple myeloma patients was correlated with the expression levels of OPN and RUNX2. Also, those expression levels were associated with bone lesion. It suggested that HGF might be one of regulators in the progression of osteogenesis. However, mechanisms by HGF-mediated c-MET activation modulate the expression of matrix metalloproteinases still remain unknown. In our study, we found that Our data show that PI3K inhibitor effectively inhibited the MMP9 mRNA expression in both OPN alone treatment and co-treatment with OPN and HGF in BMSCs. Induction of OPN and RUNX2 by HGF in MM cells could be one of the major factors for the progression of MM through interaction of MM cells and BMSCs. We suggested that induction of OPN/MMP9 strongly associated with osteoclast. For further analysis, we performed co-culture system which MM cells were grown with BMSCs obtained from MM patients’ bone marrow specimen in order to verify the role of HGF mediated c-MET activation in the progression of MM patient's osteogenesis. To explore the detail mechanisms of HGF-mediated osteogenesis, various inhibitors was used and the expression levels of a set of genes was examined using real-time PCR. Subsequently, HGF-mediated c-MET activation was regulated the expression of OPN/MMP-9 via co-effects of PIK3 activation and activation of wnt signaling pathway in BMSCs from bone marrow of MM patients. In conclusion, cross-talk between PI3K/AKT pathway and wnt singaling pathway could be one of the major factors for the progression of MM through interaction of MM cells and BMSCs. Citation Format: Hyejoo Park, Jeong In Oh, Kwang-Sung Ahn, Youngil Koh, Sung-Soo Yoon. c-MET associated with osteogenesis in multiple myeloma patients by induction of MMP9 expression by HGF in BMSCs. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4016. doi:10.1158/1538-7445.AM2015-4016
Published Version
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