Journal
BREAST CANCER RESEARCH
Volume 23, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13058-021-01423-w
Keywords
Tumor stroma; Angiogenesis; Biglycan; Tumor microenvironment; Breast cancer
Categories
Funding
- JSPS [JP18K09715, JP18H02891, JP18H02996]
- Japan Agency for Medical Research and Development (AMED) [JP18ck0106198h0003, JP19ck0106406h0002]
- Intramural Research Program of the NIH, NIDCR Molecular Biology of Bones and Teeth Section [Z01DE000379-35]
- Veterinary Resources Core (ZIC) [DE000740-05]
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The study suggests that targeting stromal biglycan may have a potent and superior anticancer effect in breast cancer patients. High expression of biglycan in breast cancer patients is associated with worse distant metastasis-free survival. Knockout of biglycan in the stroma can inhibit metastasis and tumor angiogenesis.
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.
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