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首页> 外文期刊>Journal of cellular physiology. >Extra domain A-containing fibronectin expression in Spin90-deficient fibroblasts mediates cancer-stroma interaction and promotes breast cancer progression
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Extra domain A-containing fibronectin expression in Spin90-deficient fibroblasts mediates cancer-stroma interaction and promotes breast cancer progression

机译：额外的域包含叁等奖在Spin90-deficient成纤维细胞介导cancer-stroma互动,促进乳房癌症恶化

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Cancer-associated fibroblasts (CAFs) in the tumor microenvironment play major roles in supporting cancer progression. A previous report showed that SPIN90 down-regulation is correlated with CAF activation and that SPIN 90-deficient CAFs promote breast cancer progression. However, the mechanisms that mediate cancer-stroma interaction and how such interactions regulate cancer progression are not well understood. Here, we show that extra domain A (EDA)-containing fibronectin (FN), FN(+)EDA, produced by mouse embryonic fibroblasts (MEFs) derived from Spin90-knockout (KO) mice increases their own myofibroblast differentiation, which facilitates breast cancer progression. Increased FN(+)EDA in Spin90-KO MEFs promoted fibril formation in the extracellular matrix (ECM) and specifically interacted with integrin α4β1 as the mediating receptor. Moreover, FN(+)EDA expression by Spin90-KO MEFs increased proliferation, migration, and invasion of breast cancer cells. Irigenin, a specific inhibitor of the interaction between integrin α4β1 and FN(+) EDA, significantly blocked the effects of FN(+)EDA, such as fibril formation by Spin90-KO MEFs and proliferation, migration, and invasion of breast cancer cells. In orthotopic breast cancer mouse models, irigenin injection remarkably reduced tumor growth and lung metastases. It was supported by that FN(+)EDA in assembled fibrils was accumulated in cancer stroma of human breast cancer patients in which SPIN90 expression was downregulated. Our data suggest that SPIN90 downregulation increases FN(+)EDA and promotes ECM stiffening in breast cancer stroma through an assembly of long FN(+)EDA-rich fibrils; moreover, engagement of the Integrin α4β1 receptor facilitates breast cancer progression. Inhibitory effects of irigenin on tumor growth and metastasis suggest the potential of this agent as an anticancer therapeutic.
机译：癌症相关的成纤维细胞(战乱国家)的肿瘤微环境在支持扮演重要的角色癌症的发展。与CAF SPIN90下调激活和旋转90 -战乱国家不足促进乳腺癌的进展。机制,调解cancer-stroma交互和这样的交互调节癌症进展不是很好理解。显示额外的域(EDA)包含纤连蛋白(FN)、FN (+) EDA,由鼠标胚胎成纤维细胞(mef)来自Spin90-knockout (KO)老鼠增加他们自己的myofibroblast分化,促进乳腺癌的进展。Spin90-KO mef提升原纤维形成的细胞外基质(ECM)和特别与整合素α4β1作为中介受体。Spin90-KO mef增加扩散,乳腺癌细胞迁移和入侵。Irigenin,特定的相互作用的抑制剂4之间的整合素αβ1和FN EDA (+),明显阻塞FN (+) EDA的影响,如原纤维形成的Spin90-KO mef和增殖、迁移和入侵癌细胞。模型,irigenin注入明显减少肿瘤的生长和肺转移。支持FN (+) EDA在纤维集合积累在人类乳房癌间质癌症患者SPIN90表达式表达下调。downregulation增加FN (+) EDA和促进通过一个ECM加劲在乳腺癌间质组装的FN (+) EDA-rich纤维;订婚的整合素α4β1受体促进乳腺癌的进展。irigenin对肿瘤生长的影响转移建议这个代理的潜力一个抗癌治疗。

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