Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, USA.
Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Mol Cell Endocrinol. 2017 Dec 5;457:13-19. doi: 10.1016/j.mce.2016.12.010. Epub 2016 Dec 22.
Breast cancer is one of the most frequently diagnosed malignancies in women and is characterized by predominantly estrogen dependent growth. Endocrine disruptors (EDCs) have estrogenic properties which have been shown to increase breast cancer risk. While the direct effects of EDCs on breast cancer cell biology and tumor progression have been well studied, the roles for EDCs on tumor microenvironment composition, signaling and structure are incompletely defined. Estrogen targeting of tumor stromal cells can drive paracrine signaling to breast cancer cells regulating tumorigenesis and progression. Additionally, estrogen and estrogen receptor signaling has been shown to alter breast architecture and extracellular matrix component synthesis. Unsurprisingly, EDCs have been shown to induce structural changes in the mammary gland as well as increased collagen fibers in the tissue stroma. Previous work demonstrates that human mesenchymal stem cells (hMSC) are essential components of the tumor microenvironment and are direct targets of both estrogens and EDCs. Furthermore, estrogen-stem cell cross talk has been implicated in breast cancer progression and results in increased tumor cell proliferation, angiogenesis and invasion. This review aims to dissect the possible relationship and mechanisms between EDCs, the tumor microenvironment, and breast cancer progression.
乳腺癌是女性最常见的恶性肿瘤之一，其特征主要是雌激素依赖性生长。内分泌干扰物（EDCs）具有雌激素特性，已被证明会增加乳腺癌的风险。虽然 EDCs 对乳腺癌细胞生物学和肿瘤进展的直接影响已经得到了很好的研究，但 EDCs 对肿瘤微环境组成、信号和结构的作用还不完全明确。雌激素靶向肿瘤基质细胞可以驱动旁分泌信号到乳腺癌细胞，调节肿瘤发生和进展。此外，雌激素和雌激素受体信号已被证明可以改变乳腺结构和细胞外基质成分的合成。毫不奇怪，EDCs 已被证明会诱导乳腺结构的变化，并增加组织基质中的胶原纤维。先前的工作表明，人基质干细胞（hMSC）是肿瘤微环境的重要组成部分，是雌激素和 EDCs 的直接靶点。此外，雌激素-干细胞相互作用已被牵连到乳腺癌的进展中，并导致肿瘤细胞增殖、血管生成和侵袭的增加。本综述旨在剖析 EDCs、肿瘤微环境和乳腺癌进展之间可能存在的关系和机制。
