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Title: | Mammographically dense human breast tissue stimulates MCF10DCIS.com progression to invasive lesions and metastasis | Austin Authors: | 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 | Affiliation: | Austin Health, Heidelberg, Victoria, Australia Department of Surgery, University of Melbourne, St Vincent's Hospital, Melbourne, Victoria, Australia St Vincent's Institute of Medical Research, Melbourne, Victoria, Australia Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Department of Pathology, University of Melbourne, Parkville, Victoria, Australia Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia Department of Pathology, St Vincent's Hospital, Melbourne, Victoria, Australia Northern Health, Epping, Victoria, Australia College of Health and Biomedicine, Victoria University, St Albans, Victoria, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia Australian Institute for Musculoskeletal Science (AIMSS), Victoria University, University of Melbourne and Western Health, Sunshine Hospital, St Albans, Victoria, Australia Institute of Health and Biomedical Innovation and School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia Translational Research Institute, Woolloongabba, Queensland, Australia Australian Prostate Cancer Centre - Queensland, Brisbane, Queensland, Australia Division of Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia Metastasis Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia |
Issue Date: | 25-Oct-2016 | Publication information: | Breast Cancer Research 2016; 18(1): 106 | Abstract: | 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 (nā=ā10). 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/16530 | DOI: | 10.1186/s13058-016-0767-4 | Journal: | Breast Cancer Research | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/27776557 | Type: | Journal Article | Subjects: | Breast cancer MCF10DCIS.com Mammographic density Murine biochamber |
Appears in Collections: | Journal articles |
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