Breast cancer is a prevalent hormone-dependent malignancy, and estrogens/estrogen receptor (ER) signaling are pivotal therapeutic targets in ER-positive breast cancers, where endocrine therapy has significantly improved treatment efficacy. However, the emergence of both de novo and acquired resistance to these therapies continues to pose challenges. Additionally, androgens are produced locally in breast carcinoma tissues by androgen-producing enzymes, and the androgen receptor (AR) is commonly expressed in breast cancer cells. Intratumoral androgens play a significant role in breast cancer progression and are closely linked to resistance to endocrine treatments. The tumor microenvironment, consisting of tumor cells, immune cells, fibroblasts, extracellular matrix, and blood vessels, is crucial for tumor progression. Stromal cells influence tumor progression through direct interactions with cancer cells, the secretion of soluble factors, and modulation of tumor immunity. Estrogen and androgen signaling in breast cancer cells affects the tumor microenvironment, and the expression of hormone receptors correlates with the diversity of the stromal cell profile. Notably, various stromal cells also express ER or AR, which impacts breast cancer development. This review describes how sex steroid hormones, particularly estrogens and androgens, affect stromal cells in the breast cancer microenvironment. We summarize recent findings focusing on the effects of ER/AR signaling in breast cancer cells on stromal cells, as well as the direct effects of ER/AR signaling in stromal cells.
乳腺癌是一种常见的激素依赖性恶性肿瘤，其中雌激素/雌激素受体（ER）信号通路是ER阳性乳腺癌的关键治疗靶点，内分泌治疗显著提升了该亚型患者的疗效。然而，原发性和获得性耐药的出现仍是临床面临的挑战。此外，乳腺癌组织可通过局部表达的雄激素合成酶产生雄激素，且雄激素受体（AR）在乳腺癌细胞中普遍表达。肿瘤内源性雄激素在乳腺癌进展中发挥重要作用，并与内分泌治疗耐药密切相关。肿瘤微环境由肿瘤细胞、免疫细胞、成纤维细胞、细胞外基质及血管等构成，对肿瘤进展至关重要。基质细胞通过与癌细胞直接相互作用、分泌可溶性因子及调节肿瘤免疫等方式影响肿瘤进程。乳腺癌细胞中的雌激素与雄激素信号可调控肿瘤微环境，激素受体表达水平与基质细胞谱系的多样性存在关联。值得注意的是，多种基质细胞同样表达ER或AR，这对乳腺癌发展产生影响。本综述阐述了性类固醇激素（特别是雌激素与雄激素）如何影响乳腺癌微环境中的基质细胞，重点总结了ER/AR信号在乳腺癌细胞中对基质细胞的作用，以及ER/AR信号在基质细胞中的直接效应。
Regulation of Stromal Cells by Sex Steroid Hormones in the Breast Cancer Microenvironment
肿瘤(癌症)患者之家