Establishment of a triple-negative type human breast cancer cell line that selectively metastasizes to the lung after orthotropic implantation

Abstract

Triple-negative type breast cancer (TNBC) is a challenge for today's clinical practice. To evaluate the efficacy of anticancer drugs and their combination for the treatment of patients with metastatic TNBC, an appropriate tumor model of metastatic TNBC is required. We developed a breast cancer model in mice that highly metastasizes to lung tissue using an established human TNBC cell line, MDA-MB-231. MDA-MB-231 was implanted intravenously, and lung metastasis nodes were collected. The lung metastasis nodes were then implanted into the mammary fat pad of female SCID mice, followed by surgical extraction. This procedure was repeated an additional two times, and the highly metastatic cell line, MDA-MB-231LLM, was established. After orthotropic implantation and surgical extraction, MDA-MB-231LLM selectively metastasized to the lung, and all of the mice died as a result of lung dysfunction. We then evaluated the anti-metastatic effects and survival period after treatment with S-1, a fluoropyrimidine derivative using this model. Mice were randomized into three groups on day 0. On day 29, lung metastasis was observed in all of the control mice, and the mean lung weight was 2.5 times greater than that of normal mice (P<0.01). However, after 28 days of consecutive treatment with S-1 at a dosage of 10 mg/kg with no apparent toxicity, the lung metastasis nodes were apparently fewer, and the lung weight was significantly (P<0.01) lower than that of the control. In another experiment, the survival period after treatment with S-1 was evaluated. All of the mice in the control group died as a result of lung dysfunction, and the median survival period was 35 days. However, after 28 days of consecutive treatment with S-1 (10 mg/kg), the median survival period was prolonged to 55 days (P<0.01). These results suggest that this new model will be useful for evaluating the anti-metastatic effects of chemotherapeutic agents and the survival period after chemotherapy.