High-Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single-Cell Level.
Small
; 19(6): e2206754, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36449634
ABSTRACT
Cancer cell migration represents an essential step toward metastasis and cancer deaths. However, conventional drug discovery focuses on cytotoxic and growth-inhibiting compounds rather than inhibitors of migration. Drug screening assays generally measure the average response of many cells, masking distinct cell populations that drive metastasis and resist treatments. Here, this work presents a high-throughput microfluidic cell migration platform that coordinates robotic liquid handling and computer vision for rapidly quantifying individual cellular motility. Using this innovative technology, 172 compounds were tested and a surprisingly low correlation between migration and growth inhibition was found. Notably, many compounds were found to inhibit migration of most cells while leaving fast-moving subpopulations unaffected. This work further pinpoints synergistic drug combinations, including Bortezomib and Danirixin, to stop fast-moving cells. To explain the observed cell behaviors, single-cell morphological and molecular analysis were performed. These studies establish a novel technology to identify promising migration inhibitors for cancer treatment and relevant applications.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microfluídica
/
Descoberta de Drogas
Idioma:
En
Revista:
Small
Assunto da revista:
ENGENHARIA BIOMEDICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos