Invadopodia

Invadopodia are actin-rich protrusions of the plasma membrane that are associated with degradation of the extracellular matrix in cancer invasiveness and metastasis. Very similar to podosomes, invadopodia are found in invasive cancer cells and are important for their ability to invade through the extracellular matrix, especially in cancer cell extravasation. Invadopodia can be visualized by the holes they would create in fibronectin-coated plates or by using , as co-localizing puncta of actin with Tks5. Invadopodia can also be used as a marker to quantify the invasiveness of cancer cell lines in vitro using a hyaluronic acid hydrogel assay.

In the early 1980s, researchers noticed protrusions coming from the ventral membrane of cells that had been transformed by the Rous Sarcoma Virus and that they were at the sites of cell-to-extracellular matrix (ECM) adhesion. They termed these structures podosomes, or cellular feet, but it was later noticed that degradation of the ECM was occurring at these sites and the name invadopodia was coined to highlight the invasive nature of these protrusions. Since then, researchers have often used the two names interchangeably, but it is generally accepted that podosomes are the structures involved in normal biological processes (like when immune cells need to cross tissue barriers or in bone remodeling) and invadopodia are the structures in invading cancer cells. However, there remains controversy around this nomenclature, with some scientists arguing that the two are different enough to be considered distinct structures while others argue that invadopodia are simply disregulated podosomes and cancer cells don’t simply invent new mechanisms. Due to this confusion and the high similarity between the two structures, many have begun to group the two under the collective term invadosomes.

Invadopodia have an actin core, which is surrounded by a ring structure enriched in actin-binding proteins, adhesion molecules, integrins, and scaffold proteins. Invadopodia are generally longer than podosomes, with a width of 0.5- 2.0 um and a length greater than 2 um, and they last much longer than podosomes. Invadopodia also penetrate deep into the ECM, while podosomes generally extend upward into the cytoplasm and do not cause as much ECM degradation.

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