Fibronectin assembly regulates lumen formation in breast acini,Journal of Cellular Biochemistry

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Fibronectin assembly regulates lumen formation in breast acini
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2021-01-13 , DOI: 10.1002/jcb.29885
Carina Magdaleno ₁ , Trenton House ₁ , Jogendra S Pawar ₁ , Sophia Carvalho ₁ , Narendiran Rajasekaran ₁ , Archana Varadaraj ₁

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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.

中文翻译：

纤连蛋白组装调节乳腺腺泡的管腔形成

纤连蛋白 (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。癌症中的基质 FN 硬度已被证明会影响上皮功能，例如迁移、癌症转移和上皮间质转化。上皮细胞 FN 基质在驱动此类过程中的作用仍不太清楚，但这也是本研究的重点。缺氧，即低氧张力（<5%），是影响基质细胞和上皮细胞中原纤维重组的肿瘤微环境的标志之一。在这里，使用涵盖正常、侵袭前和侵袭状态的 MCF10 乳腺上皮进展系列细胞系，我们发现缺氧期间 FN 原纤维形成减少，与这些细胞迁移潜力的减少相一致。相反，我们发现正常乳腺细胞三维腺泡生长过程中 FN 原纤维的破坏导致腺泡腔充盈。我们的数据还表明，未转化的 MCF10A 细胞中原纤维破坏后的管腔充盈会导致顶端基底极性丧失，这是侵入前和侵入性乳腺细胞系 MCF10AT 和 MCF10 DCIS.com 的特征。总体而言，这是第一项将原纤维介导的上皮细胞变化与乳腺腺泡腔清除和维持未转化生长特征的关键因素联系起来的研究。

更新日期：2021-01-13

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