Dissecting phenotypic transitions in metastatic disease via photoconversion-based isolation

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Occult metastases are a significant source of cancer relapse, but studying them is challenging due to a lack of isolation tools.
• Understanding the biology of these small, spatially distinct cell populations is crucial for developing effective therapies.

Purpose of the Study:

• To develop a novel technique for isolating discrete metastatic cell populations.
• To investigate the phenotypic and functional characteristics of spontaneously arising microcolonies in a pancreatic cancer model.

Main Methods:

• Development of PIC-IT (photoconversion-based isolation technique) for recovering cell clusters of various sizes, including single cells.
• Transcriptional profiling of isolated microcolonies from a murine pancreatic cancer model.
• Pharmacological inhibition of NF-κB pathway.

Main Results:

• PIC-IT successfully isolated microcolonies and single metastatic cells, which were previously inaccessible.
• Transcriptional profiling revealed phenotypic heterogeneity, reduced proliferation, and an inflammatory phenotype enriched in NF-κB/AP-1 signaling within microcolonies.
• NF-κB inhibition selectively depleted microcolonies, while having no impact on macrometastases.

Conclusions:

• PIC-IT is a powerful tool for the systematic investigation of metastatic heterogeneity.
• Microcolonies exhibit unique biological features and dependencies, particularly on NF-κB signaling, offering potential therapeutic targets.
• The PIC-IT technique has broad applicability for isolating and characterizing spatially distinct cell populations in various biological systems.