An Extracellular Matrix Overlay Model for Bioluminescence Microscopy to Measure Single-Cell Heterogeneous Responses to Antiandrogens in Prostate Cancer Cells

TL;DR

The paper introduces a new cell culture model to track prostate cancer cells' responses to drugs at the single-cell level using bioluminescence imaging.

Contribution

The novel extracellular matrix-Matrigel model improves single-cell tracking and viability for studying antiandrogen responses in prostate cancer cells.

Findings

The ECM-M model triples the traceability of poorly adherent prostate cancer cells.

Single-cell imaging reveals heterogeneous antiandrogen responses linked to drug IC50 values.

The model enables precise monitoring of androgen receptor modulation in diverse prostate cancer cell lines.

Abstract

Prostate cancer (PCa) displays diverse intra-tumoral traits, impacting its progression and treatment outcomes. This study aimed to refine PCa cell culture conditions for dynamic monitoring of androgen receptor (AR) activity at the single-cell level. We introduced an extracellular matrix-Matrigel (ECM-M) culture model, enhancing cellular tracking during bioluminescence single-cell imaging while improving cell viability. ECM-M notably tripled the traceability of poorly adherent PCa cells, facilitating robust single-cell tracking, without impeding substrate permeability or AR response. This model effectively monitored AR modulation by antiandrogens across various PCa cell lines. Single-cell imaging unveiled heterogeneous antiandrogen responses within populations, correlating non-responsive cell proportions with drug IC50 values. Integrating ECM-M culture with the PSEBC-TSTA biosensor enabled precise characterization of ARi responsiveness within diverse cell populations. Our ECM-M model stands as a promising tool to assess heterogeneous single-cell treatment responses in cancer, offering insights to link drug responses to intracellular signaling dynamics. This approach enhances our comprehension of the nuanced and dynamic nature of PCa treatment responses.

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