Abstract
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. 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." In vitro, DT cells were characterized by proliferation assays, colony formation assays, protein, and gene expression profiling, including PAM50 predictor analysis. In vivo, tumorigenic and metastatic potential of DT cultures was assessed in NOD/SCID and NSG mice. These cellular models differ from recently developed patient-derived xenograft models in that they can be used for both in vitro and in vivo studies. PAM50 predictor analysis showed DT cultures similar to their paired primary tumor and as belonging to the basal and Her2-enriched 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. Three DT cultures comprised of cancer-associated fibroblasts (CAFs) were isolated from luminal A, Her2-enriched, and basal primary tumors. Among the DT cells are those that are tumorigenic and metastatic in immunosuppressed mice, offering novel cellular models of ER-negative breast cancer subtypes. A group of CAFs provide tumor subtype-specific components of the tumor microenvironment (TME). Altogether, these DT cultures provide closer-to-primary cellular models for the study of breast cancer pathogenesis, metastasis, and TME.
Original language | English (US) |
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Pages (from-to) | 503-517 |
Number of pages | 15 |
Journal | Breast Cancer Research and Treatment |
Volume | 144 |
Issue number | 3 |
DOIs | |
State | Published - Apr 2014 |
Externally published | Yes |
Bibliographical note
Funding Information:Acknowledgments This project was supported by the NIH Grant 1R01 CA113674 and The Bankhead Coley Cancer Research Program Pre SPORE Grant 09BW-04 to DEA. Award Number T32CA119929 from the National Cancer Institute supported KDE. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institute of Health. This project was also supported by the BCRF funds to MEL. The authors would like to thank Ms. Sonja Dean and Dr. Ayse Burcu Ergonul (University of Miami) and Dr. James Rae (University of Michigan) for valuable discussions.
Keywords
- ER-negative breast cancer
- Metastatic xenograft models
- Primary cultures
- Tumors