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Updated: Oct 19, 2025
Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel
Published on: May 14, 2018
Selective and Marked Blockade of Endothelial Sprouting Behavior Using Paclitaxel and Related Pharmacologic Agents
Prisca K Lin1, Jocelynda Salvador1, Jun Xie2
1Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida School of Medicine, Tampa, Florida.
Abstract:
Whether alterations in the microtubule cytoskeleton affect the ability of endothelial cells (ECs) to sprout and form branching networks of tubes was investigated in this study. Bioassays of human EC tubulogenesis, where both sprouting behavior and lumen formation can be rigorously evaluated, were used to demonstrate that addition of the microtubule-stabilizing drugs, paclitaxel, docetaxel, ixabepilone, and epothilone B, completely interferes with EC tip cells and sprouting behavior, while allowing for EC lumen formation. In bioassays mimicking vasculogenesis using single or aggregated ECs, these drugs induce ring-like lumens from single cells or cyst-like spherical lumens from multicellular aggregates with no evidence of EC sprouting behavior. Remarkably, treatment of these cultures with a low dose of the microtubule-destabilizing drug, vinblastine, led to an identical result, with complete blockade of EC sprouting, but allowing for EC lumen formation. Administration of paclitaxel in vivo markedly interfered with angiogenic sprouting behavior in developing mouse retina, providing corroboration. These findings reveal novel biological activities for pharmacologic agents that are widely utilized in multidrug chemotherapeutic regimens for the treatment of human malignant cancers. Overall, this work demonstrates that manipulation of microtubule stability selectively interferes with the ability of ECs to sprout, a necessary step to initiate and form branched capillary tube networks.
Insights
Microtubule-stabilizing drugs block endothelial cell (EC) sprouting, a key step in blood vessel formation. This research shows how manipulating microtubule stability impacts angiogenesis, with implications for cancer therapies.
Area of Science:
- Cell Biology
- Angiogenesis Research
- Cancer Therapeutics
Background:
- Endothelial cells (ECs) form new blood vessels through sprouting and lumen formation.
- The role of the microtubule cytoskeleton in EC sprouting and tubulogenesis is not fully understood.
- Microtubule-targeting agents are widely used in cancer chemotherapy.
Purpose of the Study:
- To investigate how alterations in the microtubule cytoskeleton affect endothelial cell (EC) sprouting and tube network formation.
- To determine the specific effects of microtubule-stabilizing and -destabilizing drugs on EC behavior.
- To assess the in vivo relevance of these findings in a developing mouse retina model.
Main Methods:
- Utilized human EC tubulogenesis bioassays to evaluate sprouting and lumen formation.
- Administered microtubule-stabilizing drugs (paclitaxel, docetaxel, ixabepilone, epothilone B) and a microtubule-destabilizing drug (vinblastine).
- Performed in vivo experiments using the developing mouse retina model.
Main Results:
- Microtubule-stabilizing drugs completely inhibited EC sprouting while allowing lumen formation.
- Both single and aggregated ECs formed lumens without sprouting when treated with these drugs.
- Vinblastine also blocked EC sprouting, yielding similar lumen formation.
- In vivo, paclitaxel significantly interfered with angiogenic sprouting in the mouse retina.
Conclusions:
- Manipulation of microtubule stability selectively inhibits EC sprouting, a crucial step for initiating branched capillary networks.
- These findings reveal new biological activities for common chemotherapeutic agents.
- Targeting microtubule dynamics offers a potential strategy to control angiogenesis in cancer treatment.
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