a Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine , Chinese Academy of Medical Sciences and Peking Union Medical College , Tianjin , China.
b Department of Endocrinology and Metabolism, Xijing Hospital , The Fourth Military Medical University , Xi'an , China.
Cell Cycle. 2018;17(16):2027-2040. doi: 10.1080/15384101.2018.1511510. Epub 2018 Sep 18.
The heterogeneity in human breast cancer poses a challenge for effective treatment. Better understanding of tumor initiation and development will help to resolve this problem. Current models explaining intratumoral diversity include cancer stem cells, clonal evolution and cancer cell dedifferentiation and reprogramming. Herein, a new model, cancer transmission, is proposed to explain cancer heterogeneity. We found breast cancer cells (MCF10A.NeuT) were capable of transforming normal mammary epithelial cells (MCF10A). The transformed cells exhibited cancerous properties including enhanced proliferation and migration, loss of apical-basal polarity and depolarized acini structure associated with epithelial-mesenchymal transition (EMT). The transformed MCF10A cells displayed distinct EMT characteristics compared to parental cells. We further showed that cancer cell-secreted factors were sufficient to induce cancerous transformation of normal cells. Furthermore, transformed cells were resistant to radiation treatment, providing new insights into mechanisms underlying therapeutic resistance.
人类乳腺癌的异质性对有效治疗构成了挑战。更好地了解肿瘤的发生和发展将有助于解决这个问题。目前解释肿瘤内异质性的模型包括癌症干细胞、克隆进化以及癌细胞去分化和重编程。在此，提出了一种新的模型——癌症传播，以解释癌症的异质性。我们发现乳腺癌细胞（MCF10A.NeuT）能够转化正常乳腺上皮细胞（MCF10A）。转化后的细胞表现出癌症特性，包括增强的增殖和迁移、顶端-基底极性丧失以及与上皮-间充质转化（EMT）相关的去极化小腔结构。与亲本细胞相比，转化的 MCF10A 细胞表现出明显的 EMT 特征。我们进一步表明，癌细胞分泌的因子足以诱导正常细胞的癌变转化。此外，转化细胞对放射治疗具有抗性，为治疗抵抗的机制提供了新的见解。
