DOI: 10.1073/pnas.0703446104. High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish

High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish

10.1073/pnas.0703446104

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Cell metastasis is a highly dynamic process that occurs in multiple steps. Understanding this process has been limited by the inability to visualize tumor cell behavior in real time by using animal models. Here, we employ translucent zebrafish and high-resolution confocal microscopy to study how human cancer cells invade in tissues, induce angiogenesis, and interact with newly formed vessels. We use this system to study how the human metastatic geneRhoCpromotes the initial steps of metastasis. We find thatRhoCexpression induces a primitive amoeboid-like cell invasion characterized by the formation of dynamic membrane protrusions and blebs. Surprisingly, these structures penetrate the blood vessel wall exclusively at sites of vascular remodeling and not at regions of existing intact vessels. This process requires tumor cells to secrete VEGF, which induces vascular openings, which in turn, serve as portholes allowing access ofRhoC-expressing cells to the blood system. Our results support a model in which the early steps in intravasation and metastasis require two independent events: (i) dynamic regulation of the actin/myosin cytoskeleton within the tumor cell to form protrusive structures and (ii) vascular permeablization and vessel remodeling. The integration of zebrafish transgenic technology with human cancer biology may aid in the development of cancer models that target specific organs, tissues, or cell types within the tumors. Zebrafish could also provide a cost-effective means for the rapid development of therapeutic agents directed at blocking human cancer progression and tumor-induced angiogenesis.

Bibliography

Stoletov, K., Montel, V., Lester, R. D., Gonias, S. L., & Klemke, R. (2007). High-resolution imaging of the dynamic tumor cellâvascular interface in transparent zebrafish. Proceedings of the National Academy of Sciences, 104(44), 17406â17411.

Authors 5

Konstantin Stoletov (first)
Valerie Montel (additional)
Robin D. Lester (additional)
Steven L. Gonias (additional)
Richard Klemke (additional)

References 42 Referenced 280

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Dates

Type	When
Created	17 years, 10 months ago (Oct. 22, 2007, 7:11 p.m.)
Deposited	1 year, 6 months ago (Feb. 18, 2024, 11:09 a.m.)
Indexed	1 day, 8 hours ago (Sept. 4, 2025, 10:25 a.m.)
Issued	17 years, 10 months ago (Oct. 30, 2007)
Published	17 years, 10 months ago (Oct. 30, 2007)
Published Online	17 years, 10 months ago (Oct. 30, 2007)
Published Print	17 years, 10 months ago (Oct. 30, 2007)

Funders 0

None

BibTeX

@article{Stoletov_2007, title={High-resolution imaging of the dynamic tumor cell–vascular interface in transparent zebrafish}, volume={104}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0703446104}, DOI={10.1073/pnas.0703446104}, number={44}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Stoletov, Konstantin and Montel, Valerie and Lester, Robin D. and Gonias, Steven L. and Klemke, Richard}, year={2007}, month=oct, pages={17406–17411} }

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