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Updated: Jul 27, 2026
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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
Lamellipodia in invasion.
J S Condeelis1, J B Wyckoff, M Bailly
1Department of Anatomy and Structural Biology and the Intravital Imaging Program, Analytical Imaging Facility, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Seminars in Cancer Biology
|April 27, 2001
Summary
Metastatic tumor cells orient towards blood vessels, guided by chemical signals. This process involves cell extensions called lamellipodia, driven by specific molecular pathways and actin dynamics.
Area of Science:
- Cell biology
- Cancer research
- Molecular mechanisms
Background:
- Metastatic tumor cells exhibit directional movement crucial for invasion and spread.
- Chemotaxis, or cell movement in response to chemical gradients, is a key driver of metastasis.
- Epidermal Growth Factor (EGF) is a known chemoattractant for various cell types, including tumor cells.
Purpose of the Study:
- To investigate the in vivo orientation of metastatic tumor cells relative to blood vessels.
- To elucidate the molecular mechanisms underlying tumor cell chemotaxis towards EGF.
- To identify key signaling pathways and cytoskeletal components involved in lamellipod extension during chemotaxis.
Main Methods:
- Utilized in vivo imaging of Green Fluorescent Protein (GFP)-labeled metastatic tumor cells.
- Analyzed the distribution and internalization of Epidermal Growth Factor Receptors (EGFR).
- Assessed the role of Phosphoinositide 3-kinase (PI-3K) alpha p110 isoform.
- Investigated the involvement of the Arp2/3 complex and cofilin in actin dynamics.
Main Results:
- GFP-labeled metastatic tumor cells were observed to orient towards blood vessels in vivo.
- Tumor cell orientation in response to EGF initiates with lamellipod extension.
- EGF receptor distribution was uniform on the plasma membrane, with internalized receptors accumulating near the EGF source.
- The alpha p110 isoform of PI-3 kinase was found to be essential for this process.
- Lamellipod protrusion was dependent on the synergistic action of the Arp2/3 complex and cofilin for filamentous actin generation.
Conclusions:
- Metastatic tumor cells display directed migration towards blood vessels, suggesting a role in extravasation.
- Tumor cell chemotaxis towards EGF involves specific receptor dynamics and intracellular signaling.
- PI-3K signaling and actin remodeling machinery are critical for EGF-induced lamellipod extension and directed cell migration.
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