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Updated: Apr 25, 2026
MAME Models for 4D Live-cell Imaging of Tumor: Microenvironment Interactions that Impact Malignant Progression
Published on: February 17, 2012
In vivo proteomic imaging analysis of caveolae reveals pumping system to penetrate solid tumors
Phil Oh1, Jacqueline E Testa1, Per Borgstrom2
11] Proteogenomics Research Institute for Systems Medicine, San Diego, California, USA. [2] Sidney Kimmel Cancer Center, San Diego, California, USA.
Abstract:
Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrate tumors. A post-translationally modified form of annexin A1 (AnnA1) is selectively concentrated in human and rodent tumor caveolae. To follow trafficking, we generated a specific AnnA1 antibody that targets caveolae in the tumor endothelium. Intravital microscopy of caveolae-immunotargeted fluorophores even at low intravenous doses showed rapid and robust pumping across the endothelium to enter mammary, prostate and lung tumors. Within 1 h, the fluorescence signal concentrated throughout tumors to exceed the peak levels in blood. This transvascular pumping required the expression of caveolin 1 and annexin A1. Tumor uptake with other antibodies were >100-fold less. This proteomic imaging strategy reveals a unique target, antibody and caveolae pumping system for solid tumor penetration.
Insights
Researchers discovered a new way for imaging and therapeutic agents to enter solid tumors. They identified a specific protein, annexin A1 (AnnA1), that acts as a portal in tumor blood vessels, enhancing delivery.
Area of Science:
- Oncology
- Biomedical Engineering
- Molecular Imaging
Background:
- Solid tumors possess biological barriers hindering the delivery of imaging and therapeutic agents.
- Effective tumor penetration is crucial for improving diagnostic accuracy and treatment efficacy.
Purpose of the Study:
- To identify and characterize novel mechanisms for enhanced drug and imaging agent delivery across the blood-tumor barrier.
- To discover a targetable pathway for improved tumor infiltration.
Main Methods:
- Integrated proteomic and imaging analyses of caveolae at the blood-tumor interface.
- Development of an antibody targeting a modified form of annexin A1 (AnnA1) concentrated in tumor caveolae.
- Intravital microscopy to track fluorophore-conjugated antibody trafficking in vivo.
Main Results:
- Identified a post-translationally modified form of annexin A1 (AnnA1) selectively concentrated in tumor caveolae.
- Demonstrated rapid and robust transendothelial transport of AnnA1-targeted fluorophores into various solid tumors (mammary, prostate, lung).
- Observed >100-fold higher tumor uptake with AnnA1-targeted antibodies compared to others, dependent on caveolin 1 and AnnA1 expression.
Conclusions:
- Revealed an active transendothelial portal system mediated by caveolae and annexin A1 for solid tumor infiltration.
- Established a novel proteomic imaging strategy targeting caveolae for enhanced tumor penetration.
- Highlighted a unique target, antibody, and delivery system for overcoming biological barriers in solid tumors.
