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    Title: Thrombospondin enhances RANKL-dependent osteoclastogenesis and facilitates lung cancer bone metastasis
    Authors: Wang, Maofeng;Wang, Maofeng;Ch, Chia-Chia;Chao, Chia-Chia;陳?均;Liu, Po-I.;Liu, Po-I.;Yang, Yi-Chen;Yang, Yi-Chen;Su, Chen-Ming;Su, Chen-Ming;黃偉謙;Huang, Wei-Chien;湯智昕;Chih-Hsin;Tang
    Contributors: 生物科技學系
    Date: 2019-05
    Issue Date: 2019-11-08 11:49:27 (UTC+8)
    Abstract: Lung cancers have a predilection for metastasizing to bone. The matricellular glycoprotein thrombospondin (TSP)-2 regulates multiple biological functions and has a critical role in tumor development and metastasis, although its effects are uncertain in lung cancer bone metastasis. This study demonstrates that TSP-2 expression is highly correlated with lung cancer tumor stage and that the TSP-2 neutralizing antibody reduces osteoclast formation in conditioned medium obtained from lung cancer cells. We also found that TSP-2 promotes osteoclastogenesis through the RANKL-dependent pathway and that TSP-2-mediated osteoclastogenesis involves the transactivation of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) via the inhibition of miR-486-3p expression. Osteoblasts played a critical role in osteoclast differentiation and incubation of osteoblasts with TSP-2 altered the RANKL:OPG ratio. Furthermore, TSP-2 knockdown inhibited lung cancer osteolytic metastasis in vivo. TSP-2 appears to be worth targeting for the prevention of bone metastasis in lung cancer.
    Appears in Collections:[Department of Biotechnology] Journal Article

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