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Status |
Public on Aug 22, 2014 |
Title |
Primary breast tumor-derived cellular models: characterization of tumorigenic, metastatic, and cancer-associated fibroblasts in dissociated tumor (DT) cultures |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
The study of breast cancer pathogenesis relies heavily on the use of established cell lines often derived from metastatic lesions, which while having significantly contributed to the knowledge of breast cancer biology may inadvertently limit the understanding of the mechanisms governing the metastatic process. Our goal was to establish primary cultures from dissociation of breast tumors in order to provide cellular models that may better recapitulate breast cancer pathogenesis and the metastatic process. These cellular models differ from recently developed patient derived xenograft models (PDX) in that they can be used for both in vitro and in vivo studies. Here we report the characterization of six cellular models derived from the dissociation of primary breast tumor specimens, referred to as “dissociated tumor (DT) cells”. Among the DT cells are those that are tumorigenic and metastatic in immunosuppressed mice, and a group of cancer-associated fibroblasts (CAFs). In vitro, DT cells were characterized by proliferation assays, colony formation assays, protein and gene expression profiling, including PAM50 predictor analysis. The latter showed DT cultures similar to their paired primary tumor and as belonging to the basal and Her2-enriched subtypes, offering novel cellular models of these ER-negative breast cancer subtypes. In vivo, three DT cultures are tumorigenic in NOD/SCID and NSG mice, and one of these is metastatic to lymph nodes and lung after orthotopic inoculation into the mammary fat pad, without excision of the primary tumor. DT cultures comprised of CAFs were isolated from luminal-A, Her2-enriched and basal primary tumors, providing subtype-specific components of the tumor microenvironment. Altogether, these DT cultures provide closer-to-primary cellular models for the study of breast cancer pathogenesis, metastasis and tumor microenvironment.
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Overall design |
reference x sample
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Contributor(s) |
El-Ashry D |
Citation(s) |
24567196 |
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Submission date |
Feb 17, 2014 |
Last update date |
Jul 17, 2015 |
Contact name |
Charles M. Perou |
E-mail(s) |
[email protected]
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Organization name |
University of North Carolina at Chapel Hill
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Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
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Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
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City |
Chapel Hill |
State/province |
NC |
ZIP/Postal code |
27599-7264 |
Country |
USA |
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Platforms (2) |
GPL7504 |
Agilent Axon scanner UNC custom 4X44K without Virus |
GPL10481 |
Agilent-scanner-UNC-custom-4X44K-without-Virus |
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Samples (12)
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Relations |
BioProject |
PRJNA238652 |
Supplementary data files not provided |
Processed data included within Sample table |
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