Imaging and quantifying the dynamics of tumor-associated proteolysis

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Protease roles in cancer are complex and vary by cancer stage.
• Tumor-associated cells and tumor cells contribute to tumor proteolysis.
• Causal roles and critical substrates of many proteases in vivo remain poorly understood.

Purpose of the Study:

• To develop and utilize live cell assays for imaging protease activity.
• To quantify proteolysis dynamics in tumor cells and their microenvironment.
• To establish in vitro models for studying tumor proteolysis and cell interactions.

Main Methods:

• Live cell imaging assays for proteolysis.
• Protocols for quantifying proteolysis.
• In vitro mammary gland model to study microenvironment interactions.
• Co-culture assays with tumor cells and microenvironment cells.

Main Results:

• Demonstrated dynamic proteolysis by tumor cells alone and in co-culture.
• Utilized a mammary gland model to assess microenvironment effects on tumor proteolysis.
• Established methods for quantifying protease contributions from different cell types.

Conclusions:

• Live cell imaging and in vitro models are crucial for defining protease functions in cancer.
• These assays and models can identify proteolytic pathways as therapeutic targets.
• Developed tools facilitate the screening of potential therapeutic targets and imaging probes.