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Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
Published on: May 14, 2016
Disrupting tumor onset and growth via selective cell tagging (SeCT) therapy
Kenward Vong1,2, Tsuyoshi Tahara3,4, Sayaka Urano1
1Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Abstract:
This study presents the early framework of selective cell tagging (SeCT) therapy, which is the concept of preferentially labeling specific cells in vivo with chemical moieties that can elicit a therapeutic response. Using glycosylated artificial metalloenzyme (GArM)-based protein labeling, this study reports two separate functional strategies. In one approach, early tumor onset can be suppressed by tagging cancer cells in living mice with an integrin-blocking cyclic-Arg-Gly-Asp (cRGD) moiety, thereby disrupting cell adhesion onto the extracellular matrix. In another approach, tumor growth in mice can be reduced by tagging with a cytotoxic doxorubicin moiety. Subsequent cell death occurs following internalization and drug release. Overall, experiments have shown that mouse populations receiving the mixture of SeCT labeling reagents exhibited a significant delay/reduction in tumor onset and growth compared with controls. Highlighting its adaptability, this work represents a foundational step for further development of SeCT therapy and its potential therapeutic applications.
Insights
Selective cell tagging (SeCT) therapy uses targeted labeling to disrupt cancer cell adhesion or deliver cytotoxic drugs, significantly delaying tumor onset and growth in mice.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Cancer Research
Background:
- Selective cell tagging (SeCT) therapy is an emerging concept for in vivo cell labeling.
- Glycosylated artificial metalloenzymes (GArMs) offer a platform for targeted protein labeling.
Purpose of the Study:
- To present the early framework of SeCT therapy.
- To demonstrate two functional strategies for SeCT using GArM-based protein labeling.
Main Methods:
- Utilized GArM-based protein labeling for selective cell tagging in vivo.
- Employed an integrin-blocking cyclic-Arg-Gly-Asp (cRGD) moiety to disrupt cancer cell adhesion.
- Administered doxorubicin moiety for targeted cytotoxic drug delivery to cancer cells.
Main Results:
- Tagging cancer cells with cRGD suppressed early tumor onset by disrupting extracellular matrix adhesion.
- Tagging cancer cells with doxorubicin reduced tumor growth via internalization and drug release.
- Mice treated with SeCT reagents showed significant delays/reductions in tumor onset and growth compared to controls.
Conclusions:
- SeCT therapy demonstrates adaptability and potential for therapeutic applications.
- This foundational work paves the way for further development of SeCT strategies.
- Targeted in vivo cell labeling offers a promising approach for cancer treatment.
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