Single Cells to Spheres: Microfluidic Assays for Characterization of Cancer Stem-like Cells.

Microfluidics;Cancer Stem Cells;Single Cells;Mammospheres;Breast & Ovarian Cancer;Biomedical Engineering;Engineering;Biomedical Engineering

Ingram, Patrick NealLee, Somin Eunice ;

University of Michigan

关键词: Microfluidics;    Cancer Stem Cells;    Single Cells;    Mammospheres;    Breast & Ovarian Cancer;    Biomedical Engineering;    Engineering;    Biomedical Engineering;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/113408/pni_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

The cancer stem-like cell (CSC) model proposes that a small subset of stem-like cells are necessary to sustain cancer growth. CSC are resistant to traditional therapy and capable of division to give rise to a heterogeneous population to recapitulate tumors. Therapeutics which target CSC have shown potential to drastically improve patient survival. However, CSC are difficult to study as they are rare, transient, and difficult to culture. Additionally, conventional bulk assays, such as drug screens that measure success through reduction of total cell number, average out the behavior of rare but important sub-populations like CSC. There is a clear need to provide single cell tools to expedite the characterization of CSC and the development of CSC based therapies. As such, we have focused on the development and use of robust, user-friendly high throughput single cell microfluidic assays for the study of CSC. In adherent single cell assays of ovarian cancer, we have examined CSC behavior and biological factors controlling division and differentiation. It was seen that ovarian CSC exist in distinct hierarchies with possible rare de-differentiation events. In separate experiments, it was shown that bone morphogenetic protein 2 and epidermal growth factor-like protein 6 modulate self-renewal and asymmetric division, respectively. With the same approach, we screened novel therapeutics for their CSC targeting potential. Through the development and integration of novel surface coatings, we have also developed suspension based single cell derived sphere devices for marker free identification and characterization of CSC in breast cancer. We have demonstrated the use of this on-chip mammosphere assay for CSC identification, genetic analysis, stromal interactions through the use of conditioned media, and finally marker-free drug screening.