Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.
Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters. Subsequently, UACC-893, BT.20, or MDA.MB.453 were co-cultured with fibroblasts for 9 days. Co-cultures resulted in the generation of breast cancer histoid (BCH) with cancer cells showing the invasion of fibroblast spheroids, which were visualized by immunohistochemical (IHC) staining of sections (4 µm thick) of BCH. A reproducible quantitative expression of C-erbB.2 was detected in UACC-893 cancer cells in BCH sections by IHC staining and the Automated Cellular Imaging System. BCH sections also consistently exhibited qualitative expression of pancytokeratins, p53, Ki-67, or E-cadherin in cancer cells and that of vimentin or GSTPi in fibroblasts, fibronectin in the basement membrane and collagen IV in the extracellular matrix. The expression of the protein analytes and cellular architecture of BCH were markedly similar to those of breast cancer tissue.
Molecular Pathology Program, Huntington Medical Research Institutes, Pasadena, California 91101, USA.
Pavinder
P
Kaur
Brenda
B
Ward
Baisakhi
B
Saha
Lillian
L
Young
Susan
S
Groshen
Geza
G
Techy
Yani
Y
Lu
Roscoe
R
Atkinson
Clive R
CR
Taylor
Marylou
M
Ingram
S Ashraf
SA
Imam
D019149:Bioreactors; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D059016:Tumor Microenvironment
D018719:Erb-b2 Receptor Tyrosine Kinases