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Lumican 可有效调节乳腺癌细胞中雌激素受体相关的功能特性、细胞外基质效应物的表达和上皮间质转化。

Lumican effectively regulates the estrogen receptors-associated functional properties of breast cancer cells, expression of matrix effectors and epithelial-to-mesenchymal transition.

机构信息

Université de Reims Champagne Ardenne, Laboratoire de Biochimie Médicale et Biologie Moléculaire, Reims, France.

Biochemistry, Biochemical Analysis &Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.

出版信息

Sci Rep. 2017 Mar 23;7:45138. doi: 10.1038/srep45138.

Abstract

Lumican is a small leucine-rich proteoglycan that has been shown to contribute in several physiological processes, but also to exert anticancer activity. On the other hand, it has been recently shown that knockdown of the estrogen receptor α (ERα) in low invasive MCF-7 (ERα+) breast cancer cells and the suppression of ERβ in highly aggressive MDA-MB-231 (ERβ+) cells significantly alter the functional properties of breast cancer cells and the gene expression profile of matrix macromolecules related to cancer progression and cell morphology. In this report, we evaluated the effects of lumican in respect to the ERs-associated breast cancer cell behaviour, before and after suppression of ERs, using scanning electron and confocal microscopies, qPCR and functional assays. Our data pinpointed that lumican significantly attenuated cell functional properties, including proliferation, migration and invasion. Furthermore, it modified cell morphology, inducing cell-cell junctions, evoked EMT/MET reprogramming and suppressed the expression of major matrix effectors (matrix metalloproteinases and EGFR) implicated in breast cancer progression. The effects of lumican were found to be related to the type of breast cancer cells and the ERα/β type. These data support the anticancer activity of lumican and open a new area for the pharmacological targeting of the invasive breast cancer.

摘要

赖氨酰聚糖蛋白是一种富含亮氨酸的小型蛋白聚糖,已被证明在多种生理过程中发挥作用,但也具有抗癌活性。另一方面,最近的研究表明,敲低低侵袭性 MCF-7(ERα+)乳腺癌细胞中的雌激素受体α(ERα)和抑制高度侵袭性 MDA-MB-231(ERβ+)细胞中的 ERβ,会显著改变乳腺癌细胞的功能特性和与癌症进展和细胞形态相关的基质大分子的基因表达谱。在本报告中,我们使用扫描电子显微镜和共聚焦显微镜、qPCR 和功能测定,评估了赖氨酰聚糖蛋白在抑制 ERs 前后对与 ERs 相关的乳腺癌细胞行为的影响。我们的数据指出,赖氨酰聚糖蛋白显著减弱了细胞的功能特性,包括增殖、迁移和侵袭。此外,它还改变了细胞形态,诱导细胞-细胞连接,引发 EMT/MET 重编程,并抑制了与乳腺癌进展相关的主要基质效应物(基质金属蛋白酶和 EGFR)的表达。赖氨酰聚糖蛋白的作用与乳腺癌细胞的类型和 ERα/β 类型有关。这些数据支持赖氨酰聚糖蛋白的抗癌活性,并为侵袭性乳腺癌的药物靶向治疗开辟了新的领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b39/5362815/40fa688a474b/srep45138-f1.jpg

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