Related Experiment Video
Updated: Oct 20, 2025
A Permanent Window for Investigating Cancer Metastasis to the Lung
Published on: July 1, 2021
Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital
Alessia Floerchinger1, Kendelle J Murphy1, Sharissa L Latham1
1The Garvan Institute of Medical Research, St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW 2010, Australia.
Abstract:
Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo photoswitching to track intratumoral movement, we help guide treatment scheduling in a live breast cancer setting to impair metastatic progression. We uncover altered Rac1 activity at the center versus invasive border of tumors and demonstrate enhanced Rac1 activity of cells in close proximity to live tumor vasculature using optical window imaging. We further reveal that Rac1 inhibition can enhance tumor cell vulnerability to fluid-flow-induced shear stress and therefore improves overall anti-metastatic response to therapy during transit to secondary sites such as the lung. Collectively, this study demonstrates the utility of single-cell intravital imaging in vivo to demonstrate that Rac1 inhibition can reduce tumor progression and metastases in an autochthonous setting to improve overall survival.
Insights
This study uses live imaging to show that inhibiting Rac1 activity in breast cancer cells can reduce their spread. This approach helps optimize cancer treatment and improve survival by impairing metastatic progression.
Area of Science:
- Oncology
- Cell Biology
- Biomedical Imaging
Background:
- Assessing drug response in native tissue is crucial for effective cancer therapy.
- Understanding tumor cell behavior and movement is key to preventing metastasis.
Purpose of the Study:
- To investigate the role of Rac1 activity in breast cancer metastasis using intravital imaging.
- To guide treatment scheduling for improved anti-metastatic efficacy.
Main Methods:
- Longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse.
- In vivo photoswitching for tracking intratumoral cell movement.
- Optical window imaging to observe tumor vasculature interactions.
Main Results:
- Altered Rac1 activity was observed at the tumor center versus invasive borders.
- Rac1 activity was enhanced in tumor cells near blood vessels.
- Rac1 inhibition increased tumor cell vulnerability to shear stress, reducing metastasis.
Conclusions:
- Single-cell intravital imaging is valuable for studying tumor progression in vivo.
- Rac1 inhibition can reduce breast cancer metastasis and improve survival.
- Targeting Rac1 offers a potential strategy for anti-metastatic therapy.
More Related Videos
08:52Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
08:26Live Imaging of Drug Responses in the Tumor Microenvironment in Mouse Models of Breast Cancer
Published on: March 24, 2013