Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy

Cong, Li; Maishi, Nako; Annan, Dorcas A.; Young, Marian F.; Morimoto, Hirofumi; Morimoto, Masahiro; Nam, Jin-Min; Hida, Yasuhiro; Hida, Kyoko

Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy

Cong, Li; Maishi, Nako; Annan, Dorcas A. et al.

Breast cancer research, 2021, 23(1), 51

Permalink : https://hdl.handle.net/2115/82248

このアイテムのアクセス数:475件（2026-10-10 04:07 集計）

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https://doi.org/10.1186/s13058-021-01423-w			19

論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/82248
タイトル	Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy
著者	Cong, Li ; Maishi, Nako ; Annan, Dorcas A. ; Young, Marian F. ; Morimoto, Hirofumi ; Morimoto, Masahiro ; Nam, Jin-Min ; Hida, Yasuhiro ; Hida, Kyoko
著者名 Cong, Li
e-Rad_Researcher 00632423 著者名 Maishi, Nako
e-Rad_Researcher 30837240 著者名 Annan, Dorcas A.
著者名 Young, Marian F.
著者名 Morimoto, Hirofumi
著者名 Morimoto, Masahiro
e-Rad_Researcher 60414132 著者名 Nam, Jin-Min
e-Rad_Researcher 30399919 著者名 Hida, Yasuhiro
e-Rad_Researcher 40399952 著者名 Hida, Kyoko
言語	英語
キーワード	Tumor stroma
	Angiogenesis
	Biglycan
	Tumor microenvironment
	Breast cancer
発行日	2021-05-10
出版者	BioMed Central
収録物名	Breast cancer research
巻(号)	23(1)
ページ	51
抄録	Background Biglycan is a proteoglycan found in the extracellular matrix. We have previously shown that biglycan is secreted from tumor endothelial cells and induces tumor angiogenesis and metastasis. However, the function of stroma biglycan in breast cancer is still unclear. Methods Biglycan gene analysis and its prognostic values in human breast cancers were based on TCGA data. E0771 breast cancer cells were injected into WT and Bgn KO mice, respectively. Results Breast cancer patients with high biglycan expression had worse distant metastasis-free survival. Furthermore, biglycan expression was higher in the tumor stromal compartment compared to the epithelial compartment. Knockout of biglycan in the stroma (Bgn KO) in E0771 tumor-bearing mice inhibited metastasis to the lung. Bgn KO also impaired tumor angiogenesis and normalized tumor vasculature by repressing tumor necrosis factor-alpha/angiopoietin 2 signaling. Moreover, fibrosis was suppressed and CD8+ T cell infiltration was increased in tumor-bearing Bgn KO mice. Furthermore, chemotherapy drug delivery and efficacy were improved in vivo in Bgn KO mice. Conclusion Our results suggest that targeting stromal biglycan may yield a potent and superior anticancer effect in breast cancer.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	1465-5411
関連情報	PMID 33966638
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1186/s13058-021-01423-w