Primary breast tumor-derived cellular models: characterization of tumorigenic, metastatic, and cancer-associated fibroblasts in dissociated tumor (DT) cultures
| Autor: | Philip Miller, Charles M. Perou, Joeli Brinkman, Dafydd G. Thomas, J. Chuck Harrell, Dorraya El-Ashry, Kathleen M. Diehl, Thiago G. da Silva, Zheng Ao, Amy Schlater, Katherine Drews-Elger, Diana J. Azzam, Marc E. Lippman, Sanket Shah, Joyce M. Slingerland |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Primary Cell Culture Breast Neoplasms Nod Biology Metastasis Mice Breast cancer In vivo Biomarkers Tumor Tumor Cells Cultured medicine Animals Humans Neoplasm Metastasis Tumor Stem Cell Assay Cell Proliferation Tumor microenvironment Gene Expression Profiling Cell Cycle Fibroblasts medicine.disease Immunohistochemistry Primary tumor Tumor Burden Gene expression profiling Disease Models Animal Cell Transformation Neoplastic Oncology Heterografts Cancer-Associated Fibroblasts Female |
| Zdroj: | Breast Cancer Research and Treatment. 144:503-517 |
| ISSN: | 1573-7217 0167-6806 |
| DOI: | 10.1007/s10549-014-2887-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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