Hara Takamitsu, Iwadate Manabu, Tachibana Kazunoshin, Waguri Satoshi, Takenoshita Seiichi, Hamada Nobuyuki
Department of Radiological Technology, School of Radiological Technology, Gunma Prefectural College of Health Sciences, 1-323 Kamioki, 371-0052, Gunma, Maebashi, Japan.
Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, 960-1295, Fukushima, Japan.
Strahlenther Onkol. 2017 Oct;193(10):848-855. doi: 10.1007/s00066-017-1165-2. Epub 2017 Jun 22.
Metastasis represents the leading cause of breast cancer deaths, necessitating strategies for its treatment. Although radiotherapy is employed for both primary and metastatic breast cancers, the difference in their ionizing radiation response remains incompletely understood. This study is the first to compare the radioresponse of a breast cancer cell line with its metastatic variants and report that such metastatic variants are more radioresistant.
A luciferase expressing cell line was established from human basal-like breast adenocarcinoma MDA-MB-231 and underwent in vivo selections, whereby a cycle of inoculations into the left cardiac ventricle or the mammary fat pad of athymic nude mice, isolation of metastases to the bone, lung and lymph nodes visualized with bioluminescence imaging, and expansion of obtained cells was repeated twice or three times. The established metastatic cell lines were assessed for cell proliferation, wound healing, invasion, clonogenic survival, and apoptosis.
The established metastatic cell lines possessed an increased proliferative potential in vivo and were more chemotactic, invasive, and resistant to X‑ray-induced clonogenic inactivation and apoptosis in vitro.
Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.
转移是乳腺癌死亡的主要原因,因此需要制定治疗策略。尽管放疗用于原发性和转移性乳腺癌,但它们对电离辐射的反应差异仍未完全了解。本研究首次比较了乳腺癌细胞系与其转移变体的放射反应,并报告称此类转移变体具有更强的放射抗性。
从人基底样乳腺腺癌MDA-MB-231建立了一种表达荧光素酶的细胞系,并进行体内筛选,即将细胞接种到无胸腺裸鼠的左心室或乳腺脂肪垫,通过生物发光成像观察转移至骨、肺和淋巴结的情况,分离出转移灶,然后扩增获得的细胞,重复此过程两到三次。对建立的转移细胞系进行细胞增殖、伤口愈合、侵袭、克隆形成存活和凋亡评估。
建立的转移细胞系在体内具有更高的增殖潜力,在体外更具趋化性、侵袭性,且对X射线诱导的克隆形成失活和凋亡具有抗性。
乳腺癌转移至骨、肺和淋巴结会促进放射抗性。