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

Clinical & Experimental Metastasis
Yoshihiro TanimoriShozo Nishida

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.

References

May 30, 1997·The Journal of Biological Chemistry·D B WhyteJ K Pai
Feb 5, 1998·Experimental Dermatology·V M Kähäri, U Saarialho-Kere
Oct 21, 1998·Oncogene·S L CampbellC J Der
Nov 18, 1998·Current Opinion in Cell Biology·M JohnsenK Danø
Jul 27, 1999·The Journal of Biological Chemistry·H Nagase, J F Woessner
May 18, 2001·Nature·L A Liotta, E C Kohn
Jul 27, 2001·Journal of Mammary Gland Biology and Neoplasia·S Malaney, R J Daly
Apr 30, 2002·International Journal of Cancer. Journal International Du Cancer·Pia Vihinen, Veli-Matti Kähäri
Dec 13, 2002·Nature·Sandrine Etienne-Manneville, Alan Hall
Mar 29, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhaoxia LuanAndrew C Newby
Apr 19, 2003·Experimental Dermatology·E Kerkelä, U Saarialho-Kere
Oct 7, 2003·Oncogene·Thomas Bogenrieder, Meenhard Herlyn
Mar 18, 2004·The Journal of Gene Medicine·Eigo SuyamaKazunari Taira
Dec 22, 2004·The Journal of Biological Chemistry·Hua Zhou, Randall H Kramer
Apr 22, 2005·Biological Chemistry·Klaudia Giehl
Jun 30, 2005·Cancer Metastasis Reviews·Silke KuphalAnja-Katrin Bosserhoff
Apr 26, 2006·Laboratory Investigation; a Journal of Technical Methods and Pathology·Nobuyuki HonmaYutaka Aoyagi
Jan 24, 2007·Biochemical and Biophysical Research Communications·Kae HashimotoTadashi Kimura
Feb 6, 2008·IET Systems Biology·K L YeeD A Hammer
Feb 22, 2008·Recent Patents on Anti-cancer Drug Discovery·Roy BlumYoel Kloog

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Citations

Oct 25, 2011·Journal of the National Cancer Institute·Gad Rennert
Feb 22, 2012·Expert Opinion on Biological Therapy·Julie R NangiaMeghana V Trivedi
Nov 21, 2012·The Journal of Surgical Research·Hassan AlbadawiMichael T Watkins
Mar 6, 2019·Journal of Cellular Physiology·Masanobu TsubakiShozo Nishida
Jun 2, 2020·Oncotarget·Maryam Zamanian-DaryoushJoseph A DiDonato
Aug 10, 2011·Current Opinion in Supportive and Palliative Care·James R Berenson
May 29, 2018·Cancer Metastasis Reviews·József TímárE Rásó
Sep 30, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gad RennertHedy S Rennert
Jul 30, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Graziella Ribeiro de SousaMaría Sol Brassesco

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