A technique to analyse the emerging zonality of heterogeneous solid tumours

Area of Science:

• Oncology
• Computational Biology
• Tumor Microenvironment Dynamics

Background:

• Tumor heterogeneity is a hallmark of cancer, influencing treatment response and progression.
• Understanding the spatial organization of clonal subpopulations is crucial for cancer research.
• Current methods may lack the resolution to track emergent spatial patterns in vivo.

Purpose of the Study:

• To develop and validate a novel technique for analyzing the time-dependent emergence of clonal regions in heterogeneous tumors.
• To quantify the spatial self-organization of distinct tumor subpopulations.
• To investigate factors influencing the rate of spatial organization, such as compositional stability.

Main Methods:

• In vivo xenograft models using dichotomous tumor subpopulations (Clones A and D).
• Frequent sampling of tumor volume and composition.
• Enzymatic disaggregation of tumor cross-sections into single cells for compositional analysis.
• Statistical analysis of subpopulation proportions to test for emergent zonality using goodness-of-fit tests.

Main Results:

• The developed technique successfully demonstrated the emergence of 'zonality' (regions of single subpopulations) in all tested artificial tumor admixtures.
• The rate of zone emergence was found to be dependent on the 'compositional stability' of the tumor.
• Robustness studies confirmed the reliability of the global estimator for cell proportions.

Conclusions:

• The novel technique provides a robust method for analyzing spatial organization in heterogeneous tumors over time.
• Emergent zonality is a common phenomenon in artificial tumors, influenced by intrinsic tumor properties.
• This approach offers new insights into tumor evolution and spatial dynamics.