Takamitsu Hara1, Manabu Iwadate2, Kazunoshin Tachibana3, Satoshi Waguri4, Seiichi Takenoshita5, Nobuyuki Hamada6. 1. Department of Radiological Technology, School of Radiological Technology, Gunma Prefectural College of Health Sciences, 1-323 Kamioki, 371-0052, Gunma, Maebashi, Japan. 2. Department of Thyroid and Endocrinology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, 960-1295, Fukushima, Japan. 3. Department of Breast Surgery, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, 960-1295, Fukushima, Japan. 4. Department of Anatomy and Histology, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, 960-1295, Fukushima, Japan. 5. Advanced Clinical Research Center, Fukushima Global Medical Science Center, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, 960-1295, Fukushima, Japan. 6. Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), 2-11-1 Iwado-kita, 201-8511, Tokyo, Komae, Japan. hamada-n@criepi.denken.or.jp.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION:Breast cancer metastasis to the bone, lung, and lymph nodes promotes radioresistance.
Entities:
Keywords:
Basal subtype; Breast cancer; Metastatic cancer; Primary cancer; Radioresistance
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