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Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy
| 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 | | Angiogenesis | | Biglycan | | 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 |
| URI: | http://hdl.handle.net/2115/82248 |
| 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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