Microfluidic-based human prostate-cancer-on-chip.

Area of Science:

• Biomedical Engineering
• Cancer Biology
• Microfluidics

Background:

• Current prostate cancer models inadequately represent human physiology, hindering treatment development for therapy resistance and bone metastasis.
• Existing in vitro models lack complexity, while in vivo animal models present physiological and genetic differences from humans.

Purpose of the Study:

• To develop and validate the first in vitro microfluidic human Prostate-Cancer-on-Chip (PCoC) model.
• To investigate dynamic tumor-stroma interactions, including cancer-associated fibroblast (CAF) conversion and tumor cell invasion.

Main Methods:

• Co-cultivation of human prostate cancer and stromal fibroblast cells in a microfluidic device with a porous membrane.
• Analysis of cell-cell signaling, CAF biomarker expression (αSMA, COL1A1), androgen receptor (AR) downregulation, and tumor invasion using immunofluorescence microscopy.
• Simulation of solute concentration gradients to correlate with CAF conversion levels.

Main Results:

• Prostate cancer cells induced CAF conversion in stromal fibroblasts, with conversion levels increasing along the medium flow direction.
• Tumor cells downregulated stromal AR expression, unlike in normal prostate homeostasis.
• The PCoC model demonstrated tumor cell and CAF invasion into neighboring compartments, highlighting the stroma's role in promoting metastasis.

Conclusions:

• The developed PCoC model effectively recapitulates spatiotemporal tumor-stroma interactions and multicellular responses relevant to human prostate cancer in vivo.
• This model serves as a valuable tool for dissecting prostate cancer mechanisms and exploring novel therapeutic strategies.