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Dynamic membrane remodeling at invadopodia differentiates invadopodia from podosomes
Vira V Artym1, Kazue Matsumoto, Susette C Mueller
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical School, Washington, DC 20057, USA. vartym@mail.nih.gov
European Journal of Cell Biology
|July 27, 2010
Summary
Invadopodia, crucial for cancer cell invasion, form dynamic membrane structures with actin-cortactin cores. These invasive superstructures differ significantly from macrophage podosomes, which lack such membrane protrusions.
Area of Science:
- Cell Biology
- Cancer Research
- Biophysics
Background:
- Invadopodia are actin-rich cell protrusions essential for extracellular matrix (ECM) degradation and invasion by metastatic tumor cells.
- Discrepancies between electron microscopy (long filaments) and fluorescence microscopy (actin-cortactin aggregates) have hindered understanding of invadopodia structure and regulation.
- Clarifying the relationship between membrane dynamics and the actin-cortactin core is key to understanding invadopodia function.
Purpose of the Study:
- To integrate structural descriptions of invadopodia by examining cell membrane dynamics at the cortactin core.
- To elucidate the relationship between membrane filaments and actin-cortactin aggregates in invadopodia formation.
- To differentiate invadopodia from podosomes based on membrane dynamics.
Main Methods:
- Utilized rapid live-cell high-resolution Total Internal Reflection Fluorescence (TIRF) microscopy.
- Examined cell membrane dynamics at the cortactin core of invadopodia in human carcinoma cells.
- Compared membrane behavior in invadopodia with that of macrophage podosomes.
Main Results:
- Cortactin docking to the cell membrane initiates invadopodium assembly, forming a membrane process extending towards the ECM.
- The invadopodial membrane tip exhibits dynamic ruffling and forms filament-like protrusions during maturation.
- Macrophage podosome membranes, in contrast, showed no such process- or filament-like protrusions.
Conclusions:
- A novel model of the invadopodial complex is proposed, highlighting the dynamic interplay between the actin-cortactin core and the invadopodial membrane.
- Invadopodia are defined as distinct invasive superstructures characterized by membrane undulation, ruffling, and dynamic filament formation.
- These findings distinguish invadopodia from podosomes, offering new insights into cancer cell invasion mechanisms.
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