Linking invasive motility to protein expression in single tumor cells

Area of Science:

• Oncology
• Biotechnology
• Cell Biology

Background:

• Cancer cell invasion is crucial for metastasis.
• Tumor cells exhibit heterogeneous invasive potential.
• The link between single-cell protein expression and invasion is poorly understood.

Purpose of the Study:

• To develop a platform for simultaneous measurement of single-cell invasion and protein expression.
• To investigate protein expression variations in human glioblastoma tumor-initiating cells (TICs).
• To identify molecular targets associated with cancer cell invasiveness.

Main Methods:

• A microfluidic device with tissue-like stiffness and chemokine gradients was engineered.
• Live-cell imaging tracked single-cell motility and separation within microchannels.
• In situ lysis and western blotting on the microfluidic platform enabled single-cell protein analysis.

Main Results:

• Distinct cell subpopulations based on motility were observed.
• Correlations between cell motility and Nestin/EphA2 expression were identified.
• Intra-cellular protein-protein correlations, missed by bulk assays, were discovered.

Conclusions:

• The integrated microfluidic platform links single-cell invasive traits to specific protein expression profiles.
• This approach provides novel insights into glioblastoma heterogeneity and invasiveness.
• The platform can identify potential therapeutic targets for inhibiting cancer cell invasion.