학술논문
Development and characterisation of a 3D multi-cellular in vitro model of normal human breast: a tool for cancer initiation studies.
Document Type
Academic Journal
Author
Nash CE; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.; Current address: The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.; Mavria G; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.; Baxter EW; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.; Holliday DL; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.; Tomlinson DC; Leeds Institute of Biomedical and Clinical Sciences, University of Leeds, Leeds, UK.; Treanor D; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.; Leeds Teaching Hospitals NHS Trust, Leeds, UK.; Novitskaya V; School of Cancer Sciences, University of Birmingham, Birmingham, UK.; Berditchevski F; School of Cancer Sciences, University of Birmingham, Birmingham, UK.; Hanby AM; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.; Speirs V; Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.
Source
Publisher: Impact Journals Country of Publication: United States NLM ID: 101532965 Publication Model: Print Cited Medium: Internet ISSN: 1949-2553 (Electronic) Linking ISSN: 19492553 NLM ISO Abbreviation: Oncotarget Subsets: MEDLINE
Subject
Language
English
Abstract
Multicellular 3-dimensional (3D) in vitro models of normal human breast tissue to study cancer initiation are required. We present a model incorporating three of the major functional cell types of breast, detail the phenotype and document our breast cancer initiation studies. Myoepithelial cells and fibroblasts were isolated and immortalised from breast reduction mammoplasty samples. Tri-cultures containing non-tumorigenic luminal epithelial cells HB2, or HB2 overexpressing different HER proteins, together with myoepithelial cells and fibroblasts were established in collagen I. Phenotype was assessed morphologically and immunohistochemically and compared to normal breast tissue. When all three cell types were present, polarised epithelial structures with lumens and basement membrane production were observed, akin to normal human breast tissue. Overexpression of HER2 or HER2/3 caused a significant increase in size, while HER2 overexpression resulted in development of a DCIS-like phenotype. In summary, we have developed a 3D tri-cellular model of normal human breast, amenable to comparative analysis after genetic manipulation and with potential to dissect the mechanisms behind the early stages of breast cancer initiation.