Baicalein disturbs the morphological plasticity and motility of breast adenocarcinoma cells depending on the tumour microenvironment.
Baicalein disturbs the morphological plasticity and motility of breast adenocarcinoma cells depending on the tumour microenvironment.
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黄芩素根据肿瘤微环境扰乱乳腺腺癌细胞的形态可塑性和运动性。
DOI：
10.1111/gtc.12584
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发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Kimura T. and Ishizaki T.
中科院分区：
文献类型：
--
作者：
Terabayashi T.;Hanada K.;Motani K.;Kosako H.;Yamaoka M.;Kimura T. and Ishizaki T.
在肿瘤侵袭过程中，癌细胞通过与周围环境的沟通来改变其形态和迁移方式。大量研究表明，来自非肿瘤细胞的旁分泌相互作用影响癌细胞的迁移和侵袭特性。因此，这些相互作用是抗癌治疗的潜在靶点。在这项研究中，我们证明了黄酮类成员黄芩素抑制了旁分泌相互作用促进的乳腺癌细胞的运动。首先，我们确定层粘连蛋白-332(LN-332)是乳腺上皮源性MCF10A细胞条件培养液中的主要旁分泌因子，它调节乳腺癌MDA-MB-231细胞的形态和运动。然后，我们进行了基于形态的小分子化合物筛选，结果表明，黄芩素抑制了MCF10A细胞和LN-332条件培养液诱导的MDA-MB-231细胞的形态变化和迁移活性。我们还发现，尽管Rho家族小GTP酶下游的肌动蛋白动力学没有受到影响，但黄芩素导致条件性中等处理的MDA-MB-231细胞形成更窄和不完全的片状脂。这些结果提示乳腺上皮细胞在肿瘤微环境中的重要性，促进了乳腺腺癌细胞的迁移活性，并揭示了黄芩素抑制癌细胞运动的新机制。
During tumor invasion, cancer cells change their morphology and mode of migration based on communication with the surrounding environment. Numerous studies have indicated that paracrine interactions from non‐neoplastic cells impact the migratory and invasive properties of cancer cells. Thus, these interactions are potential targets for anticancer therapies. In this study, we showed that the flavones member baicalein suppresses the motility of breast cancer cells that is promoted by paracrine interactions. First, we identified laminin‐332 (LN‐332) as a principle paracrine factor in conditioned medium from mammary epithelium‐derived MCF10A cells that regulates the morphology and motility of breast adenocarcinoma MDA‐MB‐231 cells. Then, we carried out a morphology‐based screen for small compounds, which showed that baicalein suppressed the morphological changes and migratory activity of MDA‐MB‐231 cells that were induced by conditioned medium from MCF10A cells and LN‐332. We also found that baicalein caused narrower and incomplete lamellipodia formation in conditioned medium‐treated MDA‐MB‐231 cells, although actin dynamics downstream of Rho family small GTPases were unaffected. These results suggest the importance of mammary epithelial cells in the cancer microenvironment promoting the migratory activity of breast adenocarcinoma cells and show a novel mechanism through which baicalein inhibits cancer cell motility.