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

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

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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-ɑ/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.

Original languageEnglish
Article number51
JournalBreast Cancer Research
Volume23
Issue number1
DOIs
Publication statusPublished - 12-2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Inhibition of stromal biglycan promotes normalization of the tumor microenvironment and enhances chemotherapeutic efficacy'. Together they form a unique fingerprint.

Cite this