Breast cancer research : BCR · 2016
Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Huo Cecilia W, Waltham Mark, Khoo Christine, Fox Stephen B, Hill Prue, Chen Shou, Chew Grace L, Price John T, Nguyen Chau H, Williams Elizabeth D, Henderson Michael, Thompson Erik W, Britt Kara L
Аннотация
BACKGROUND: High mammographic density (HMD) not only confers a significantly increased risk of breast cancer (BC) but also is associated with BCs of more advanced stages. However, it is unclear whether BC progression and metastasis are stimulated by HMD. We investigated whether patient-derived HMD breast tissue could stimulate the progression of MCF10DCIS.com cells compared with patient-matched low mammographic density (LMD) tissue.
METHODS: Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
RESULTS: HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
CONCLUSIONS: Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.
METHODS: Sterile breast specimens were obtained immediately after prophylactic mastectomy from high-risk women (n = 10). HMD and LMD regions of each specimen were resected under radiological guidance. Human MCF10DCIS.com cells, a model of ductal carcinoma in situ (DCIS), were implanted into silicone biochambers in the groins of severe combined immunodeficiency mice, either alone or with matched LMD or HMD tissue (1:1), and maintained for 6 weeks. We assessed biochamber weight as a measure of primary tumour growth, histological grade of the biochamber material, circulating tumour cells and metastatic burden by luciferase and histology. All statistical tests were two-sided.
RESULTS: HMD breast tissue led to increased primary tumour take, increased biochamber weight and increased proportions of high-grade DCIS and grade 3 invasive BCs compared with LMD. This correlated with an increased metastatic burden in the mice co-implanted with HMD tissue.
CONCLUSIONS: Our study is the first to explore the direct effect of HMD and LMD human breast tissue on the progression and dissemination of BC cells in vivo. The results suggest that HMD status should be a consideration in decision-making for management of patients with DCIS lesions.