Fibronectin assembly regulates lumen formation in breast acini.
Fibronectin assembly regulates lumen formation in breast acini.
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DOI：
10.1002/jcb.29885
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发表时间：
2021-05
影响因子：
4
通讯作者：
Varadaraj A
中科院分区：
文献类型：
--
作者：
Magdaleno C;House T;Pawar JS;Carvalho S;Rajasekaran N;Varadaraj A
纤维连接蛋白（FN）是一种细胞外基质（ECM）糖蛋白，可自组装成FN原纤维，形成有助于ECM硬度的FN基质。癌症中基质FN的硬度已被证明会影响上皮功能，如迁移、癌症转移和上皮向间质转化。上皮细胞FN基质在驱动这一过程中的作用尚不清楚，也是本研究的重点。低氧压（<5%）是肿瘤微环境影响间质和上皮细胞纤维重组的标志之一。在这里，我们使用MCF10乳腺上皮细胞系的进展系列，包括正常、侵袭前和侵袭状态，我们发现缺氧时FN原纤维的形成减少，与这些细胞的迁移潜力减少相一致。相反，我们发现在正常乳腺细胞的三维腺泡生长过程中FN原纤维的破坏导致腺泡腔填充。我们的数据还表明，在未转化的MCF10A细胞中，纤维断裂后的管腔填充导致根尖基底极性的丧失，这是侵袭前和侵袭性乳腺细胞系MCF10AT和MCF10 DCIS.com的特征。总的来说，这是第一个将纤维介导的上皮细胞变化作为乳腺腺泡腔清除和维持未转化生长特征的关键参与者的研究。乳腺腺泡中纤维连接蛋白原纤维断裂和管腔充盈。
Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that self‐assembles into FN fibrils, forming a FN matrix contributing to the stiffness of the ECM. Stromal FN stiffness in cancer has been shown to impact epithelial functions such as migration, cancer metastasis, and epithelial‐to‐mesenchymal transition. The role of the FN matrix of epithelial cells in driving such processes remains less well understood and is the focus of this study. Hypoxia, defined by low oxygen tension (<5%) is one of the hallmarks of tumor microenvironments impacting fibril reorganization in stromal and epithelial cells. Here, using the MCF10 breast epithelial progression series of cell lines encompassing normal, preinvasive, and invasive states, we show that FN fibril formation decreases during hypoxia, coinciding with a decrease in migratory potential of these cells. Conversely, we find that FN fibril disruption during three‐dimensional acinar growth of normal breast cells resulted in acinar luminal filling. Our data also demonstrates that the luminal filling upon fibril disruption in untransformed MCF10A cells results in a loss of apicobasal polarity, characteristic of pre‐invasive and invasive breast cell lines MCF10AT and MCF10 DCIS.com. Overall this is the first study that relates fibril‐mediated changes in epithelial cells as critical players in lumen clearing of breast acini and maintenance of the untransformed growth characteristic. Fibronectin fibril disruption and lumen filling in breast acini.
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