Abstract 6129: A scalable, non-biased screen for isolating functionally metastatic cell populations
| Autor: | Alex Lekan, Eric Glasgow, Seema Agarwal, Jerry Xiao, Kelly P. Stanton |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
education.field_of_study Population Cell Cancer Biology medicine.disease biology.organism_classification Metastasis medicine.anatomical_structure Circulating tumor cell Oncology Downregulation and upregulation medicine Cancer research Epithelial–mesenchymal transition education Zebrafish |
| Zdroj: | Cancer Research. 80:6129-6129 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Up to 90% of cancer-associated deaths are due to metastasis. Nonetheless, the mechanisms of metastasis are poorly understood, largely because of a lack of technologies to routinely and robustly isolate, propagate, and culture metastatic cells. Current cellular models for metastasis are hindered by a lack of scalability, a high cost per experiment, and the length of experiments. In this proof-of-principle study, we injected an invasive triple-negative breast cancer cell line, MDA-MB-231, into zebrafish embryos. Cells were monitored for invasion from the yolk sac into the zebrafish circulatory system, representing a cell population analogous to metastatic, circulating tumor cells. Within 5 days, cells had migrated from the primary injection site to the tail. Tails showing migration of cells were excised, digested, and the labeled human-cancer cells were propagated. Re-injection of propagated cells resulted in serial generations (F1 and F2). The time required for migration decreased with each succeeding generation; with the latest (F2) generation migrating to the tail within 24 hours. In addition to being more invasive, cells that migrated to the tail displayed a more mesenchymal phenotype compared to parental cells. Consistent with this finding, RNA-seq analysis showed an upregulation of genes involved in an epithelial to mesenchymal transition. Moreover, the highest differentially expressed genes have been independently associated with metastasis. Finally, in silico analyses demonstrated that the upregulated genes were clinically significant. Together these data provide proof-of-principle that we have established a scalable, rapid, and robust method that can provide routine access to invasive metastatic cells. The platform combines in vivo and in vitro components that can be used to isolate, enrich, and propagate metastatic cells from individual patients, and has the potential to advance basic and translational research in tumor metastasis. This cellular model relies solely on cell behavior and is a non-biased method that can be widely applied to all tumor types as it does not require specific biomarkers. In addition to providing a tool for advancing our understanding of metastases, the technology has the potential to be used in screening for drugs that specifically target metastatic cells; a critical unmet need in the treatment of human cancers. Citation Format: Jerry Xiao, Alex Lekan, Kelly Stanton, Eric Glasgow, Seema Agarwal. A scalable, non-biased screen for isolating functionally metastatic cell populations [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6129. |
| Databáze: | OpenAIRE |
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