Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP)

Mitamura, T.; Pradeep, S.; McGuire, M.; Wu, S Y; Ma, S.; Hatakeyama, H.; Lyons, Y A; Hisamatsu, T.; Noh, K.; Villar-Prados, A; Chen, X.; Ivan, C.; Rodriguez-Aguayo, C; Hu, W.; Lopez-Berestein, G; Coleman, R L; Sood, A K

Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP)

Mitamura, T.; Pradeep, S.; McGuire, M. et al.

Oncogene, 2018, 37(6), 722-731

Permalink : https://hdl.handle.net/2115/68863

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アクセス権	open access
URI	https://hdl.handle.net/2115/68863
タイトル	Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP)
その他のタイトル	Proangiogenic effects of MSMP in ovarian cancer
著者	Mitamura, T. ; Pradeep, S. ; McGuire, M. ; Wu, S Y ; Ma, S. ; Hatakeyama, H. ; Lyons, Y A ; Hisamatsu, T. ; Noh, K. ; Villar-Prados, A ; Chen, X. ; Ivan, C. ; Rodriguez-Aguayo, C ; Hu, W. ; Lopez-Berestein, G ; Coleman, R L ; Sood, A K
著者名 Mitamura, T. 著者別名 Mitamura, Takashi
著者名 Pradeep, S. 著者別名 Pradeep, Sunila
著者名 McGuire, M. 著者別名 McGuire, Michael
著者名 Wu, S Y 著者別名 Wu, Sherry
著者名 Ma, S. 著者別名 Ma, Shaolin
著者名 Hatakeyama, H. 著者別名 Hatakeyama, Hiroto
著者名 Lyons, Y A 著者別名 Lyons, Yasmin A.
著者名 Hisamatsu, T. 著者別名 Hisamatsu, Takeshi
著者名 Noh, K. 著者別名 Noh, Kyunghee
著者名 Villar-Prados, A 著者別名 Villar-Prados, Alejandro
著者名 Chen, X. 著者別名 Chen, Xiuhui
著者名 Ivan, C. 著者別名 Ivan, Cristina
著者名 Rodriguez-Aguayo, C 著者別名 Rodriguez-Aguayo, Cristian
著者名 Hu, W. 著者別名 Hu, Wei
著者名 Lopez-Berestein, G 著者別名 Lopez-Berestein, Gabriel
著者名 Coleman, R L 著者別名 Coleman, Robert L.
著者名 Sood, A K 著者別名 Sood, Anil K.
言語	英語
キーワード	MSMP
	CCR2
	anti-VEGF antibody
	human ovarian cancer
	bevacizumab
	adaptive resistance
発行日	2018-02-08
出版者	Nature Publishing Group
収録物名	Oncogene
巻(号)	37(6)
ページ	722-731
抄録	Anti-vascular endothelial growth factor (VEGF) therapy has demonstrated efficacy in treating human metastatic cancers, but therapeutic resistance is a practical limitation and most tumors eventually become unresponsive. To identify microenvironmental factors underlying the resistance of cancer to antiangiogenesis therapy, we conducted genomic analyses of intraperitoneal ovarian tumors in which adaptive resistance to anti-VEGF therapy (B20 antibody) developed. We found that expression of the microseminoprotein, prostate-associated (MSMP) gene was substantially upregulated in resistant compared with control tumors. MSMP secretion from cancer cells was induced by hypoxia, triggering MAPK signaling in endothelial cells to promote tube formation in vitro. Recruitment of the transcriptional repressor CCCTC-binding factor (CTCF) to the MSMP enhancer region was decreased by histone acetylation under hypoxic conditions in cancer cells. MSMP siRNA, delivered in vivo using the DOPC nanoliposomes, restored tumor sensitivity to anti-VEGF therapy. In ovarian cancer patients treated with bevacizumab, serum MSMP concentration increased significantly only in non-responders. These findings imply that MSMP inhibition combined with the use of antiangiogenesis drugs may be a new strategy to overcome resistance to antiangiogenesis therapy.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	0950-9232
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1038/onc.2017.348