Suppression of hyaluronan synthesis attenuates the tumorigenicity of low-grade chondrosarcoma

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Shunsuke HamadaNaoki Ishiguro

Abstract

Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant tumors. Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of an HA synthesis inhibitor, 4-methylumbelliferone (MU), on ECM formation as well as antitumor effects in chondrosarcoma. We investigated the effects of MU on rat chondrosarcoma (RCS) cells with a grade I histological malignancy in vitro and in vivo grafted model. HA binding protein (HABP) stainability on and around the RCS cells was effectively reduced with treatment of MU. ECM formation was markedly suppressed by MU at a dose of 1.0 mM. Cell proliferation was significantly reduced by MU at 24 h. Cell motility and invasion were suppressed in a dose-dependent manner by MU. No significant changes in mRNA expression of Has1-3 were observed. Furthermore, MU inhibited the growth of grafted tumors in vivo. Histologically, chondrosarcoma cells of control tumors showed a cell-clustering structure. HABP stainability was markedly decreased in the MU-treated group. These results suggest that MU...Continue Reading

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Citations

Nov 18, 2018·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Caterina FedeRaffaele De Caro
Dec 7, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·William P ShieldMotomi Enomoto-Iwamoto
Jan 5, 2020·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Yeonjung YoonJin Sook Yoon
Jun 6, 2018·Frontiers in Cell and Developmental Biology·James B McCarthyEva A Turley

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