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. 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. 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. Our results suggest that targeting stromal biglycan may yield a potent and superior anticancer effect in breast cancer.

中文翻译：

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抑制基质双糖链蛋白聚糖促进肿瘤微环境正常化并增强化疗效果


双糖链蛋白聚糖是一种存在于细胞外基质中的蛋白聚糖。我们之前已经证明双糖链蛋白聚糖是由肿瘤内皮细胞分泌并诱导肿瘤血管生成和转移。然而，基质双糖链蛋白聚糖在乳腺癌中的功能仍不清楚。 Biglycan 基因分析及其在人类乳腺癌中的预后价值基于 TCGA 数据。 E0771乳腺癌细胞分别注射到WT和Bgn KO小鼠体内。双糖链蛋白聚糖高表达的乳腺癌患者的无远处转移生存期较差。此外，与上皮区室相比，肿瘤基质区室中的双糖链蛋白聚糖表达更高。在 E0771 荷瘤小鼠的基质中敲除双糖链蛋白聚糖 (Bgn KO) 可抑制肺转移。 Bgn KO 还通过抑制肿瘤坏死因子-ɑ/血管生成素 2 信号传导来损害肿瘤血管生成并使肿瘤脉管系统正常化。此外，在荷瘤 Bgn KO 小鼠中，纤维化受到抑制，CD8+ T 细胞浸润增加。此外，Bgn KO 小鼠的体内化疗药物递送和疗效得到改善。我们的结果表明，靶向基质双糖链蛋白聚糖可能对乳腺癌产生有效且优越的抗癌作用。