白藜芦醇通过干扰肿瘤-基质细胞间通讯抑制人乳腺癌细胞的迁移、侵袭和干性。

Resveratrol suppresses migration, invasion and stemness of human breast cancer cells by interfering with tumor-stromal cross-talk.

机构信息

Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.

Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea; Cancer Research Institute, Seoul National University, Seoul, South Korea.

出版信息

Arch Biochem Biophys. 2018 Apr 2;643:62-71. doi: 10.1016/j.abb.2018.02.011. Epub 2018 Mar 15.

DOI:10.1016/j.abb.2018.02.011

PMID:29477771

Abstract

Cancer-associated fibroblasts (CAFs) constitute a major compartment of the tumor microenvironment. CAFs produce a variety of cytokines, growth factors and extracellular matrix proteins, thereby stimulating tumor progression. CAFs are distinct from normal fibroblasts for their overexpression of α-smooth muscle actin. Recent studies suggest that CAFs play an important role in proliferation and migration of cancer cells through cross-talk with them. Resveratrol (trans-3,4'5,-trihydroxystilbene), a phytoalexin present in grapes, has been reported to possess chemopreventive and chemotherapeutic activities. In the present study, we examined the effects of resveratrol on CAF-induced migration, invasion and self-renewal activity of breast cancer cells. Resveratrol inhibited proliferation, migration and invasion of human breast cancer cells treated with CAF-conditioned media (CAF-CM). Resveratrol treatment suppressed the CAF-CM-induced expression of Cyclin D1, c-Myc, MMP-2 and MMP-9. In addition, resveratrol inhibited Sox2 expression as well as activation of Akt and STAT3 induced by CAF-CM in breast cancer cells. Further, resveratrol abrogated stemness properties and reduced the expression of self-renewal signaling molecules in stem-like breast cancer cells. Taken together, the present study provides insights into the role of resveratrol in tumor microenvironment with focus on interaction between cancer cells and the hosting niche.

摘要

癌症相关成纤维细胞（CAFs）构成肿瘤微环境的主要组成部分。CAFs 产生多种细胞因子、生长因子和细胞外基质蛋白，从而刺激肿瘤的进展。CAFs 因其过度表达α-平滑肌肌动蛋白而与正常成纤维细胞不同。最近的研究表明，CAFs 通过与癌细胞的相互作用在癌细胞的增殖和迁移中发挥重要作用。白藜芦醇（trans-3,4'5,-三羟基二苯乙烯）是葡萄中的一种植物抗毒素，已被报道具有化学预防和化学治疗活性。在本研究中，我们研究了白藜芦醇对 CAF 诱导的乳腺癌细胞迁移、侵袭和自我更新活性的影响。白藜芦醇抑制了用 CAF 条件培养基（CAF-CM）处理的人乳腺癌细胞的增殖、迁移和侵袭。白藜芦醇处理抑制了 CAF-CM 诱导的 Cyclin D1、c-Myc、MMP-2 和 MMP-9 的表达。此外，白藜芦醇抑制了 CAF-CM 诱导的乳腺癌细胞中 Sox2 表达以及 Akt 和 STAT3 的激活。此外，白藜芦醇削弱了干细胞特性，并降低了干细胞样乳腺癌细胞中自我更新信号分子的表达。总之，本研究提供了关于白藜芦醇在肿瘤微环境中作用的见解，重点关注癌细胞与宿主生态位之间的相互作用。