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01.10.2010 | Research Paper

Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits tumor metastasis in mouse melanoma through suppression of the Rho/ROCK pathway

verfasst von: Yoshihiro Tanimori, Masanobu Tsubaki, Yuzuru Yamazoe, Takao Satou, Tatsuki Itoh, Yasuhiro Kidera, Masahi Yanae, Chikako Yamamoto, Junichi Kaneko, Shozo Nishida

Erschienen in: Clinical & Experimental Metastasis | Ausgabe 7/2010

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Abstract

The small GTPases of the Ras and Rho families are widely involved in tumorigenesis and metastasis. We recently showed that YM529/ONO-5920, a new developed bisphosphonate, inhibits the mevalonate pathway, is required for the prenylation of the small GTPases. In this study, we investigated whether YM529/ONO-5920 inhibits tumor cell migration, invasion, adhesion, and metastasis in B16BL6 cells, a mouse melanoma cell line. It was found that YM529/ONO-5920 significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not show anti-proliferative effects on B16BL6 cells. YM529/ONO-5920 also inhibited the expression of matrix metalloproteinases (MMPs) and very late antigens (VLAs). Furthermore, YM529/ONO-5920 suppressed Rho activation, but not activation of Ras. The results indicate that YM529/ONO-5920 suppresses the Rho/ROCK pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion and metastasis. These findings suggest that YM529/ONO-5920 has potential clinical applications for the treatment of tumour cell metastasis.

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Titel: Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits tumor metastasis in mouse melanoma through suppression of the Rho/ROCK pathway
verfasst von: Yoshihiro Tanimori
Masanobu Tsubaki
Yuzuru Yamazoe
Takao Satou
Tatsuki Itoh
Yasuhiro Kidera
Masahi Yanae
Chikako Yamamoto
Junichi Kaneko
Shozo Nishida
Publikationsdatum: 01.10.2010
Verlag: Springer Netherlands
Erschienen in: Clinical & Experimental Metastasis / Ausgabe 7/2010
Print ISSN: 0262-0898
Elektronische ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-010-9342-z

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Nitrogen-containing bisphosphonate, YM529/ONO-5920, inhibits tumor metastasis in mouse melanoma through suppression of the Rho/ROCK pathway

Abstract

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