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

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Title: Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy
Authors: Cong, Li Browse this author
Maishi, Nako Browse this author →KAKEN DB
Annan, Dorcas A. Browse this author →KAKEN DB
Young, Marian F. Browse this author
Morimoto, Hirofumi Browse this author
Morimoto, Masahiro Browse this author
Nam, Jin-Min Browse this author →KAKEN DB
Hida, Yasuhiro Browse this author →KAKEN DB
Hida, Kyoko Browse this author →KAKEN DB
Keywords: Tumor stroma
Tumor microenvironment
Breast cancer
Issue Date: 10-May-2021
Publisher: BioMed Central
Journal Title: Breast cancer research
Volume: 23
Issue: 1
Start Page: 51
Publisher DOI: 10.1186/s13058-021-01423-w
PMID: 33966638
Abstract: 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.
Type: article
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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