Release of cell fragments by invading melanoma cells

https://doi.org/10.1078/0171-9335-00394Get rights and content

Summary

Tumor cell invasion requires coordinated cell adhesion to an extracellular matrix (ECM) substrate at the leading edge and concomitant detachment at the cell rear. Known detachment mechanisms include the slow sliding of focal contacts, the detachment of adhesion receptors by affinity and avidity regulation, as well as the shedding of adhesion receptors, most notably integrins. In highly invasive melanoma cells migrating within 3D collagen matrices, β1 integrins and CD44 are released upon retraction of the trailing edge, together with ripping-off complete cell fragments to become deposited along the migration trail of remodeled matrix. Cell fragments reach a size up to 12 μm in diameter, contain cytoplasm and occasionally polymerized actin enclosed by intact cell membrane including surface β1 integrins, but do not include nuclear material. The release of cell fragments was migration dependent, as impairment of motility by a blocking anti-β1 integrin antibody also blocked cell particle release. Invasion-associated deposition of cell fragments combines the secretory-type release of vesicles with a physical mechanism of rear retraction and migration efficiency. The deposition of cell fragments may further represent a disregulated detachment strategy with implications for neoplastic cell behavior, such as the paracrine effects on neighbor cells or a negative impact on immune effector cells.

References (0)

Cited by (33)

  • Cripto-1 localizes to dynamic and shed filopodia associated with cellular migration in glioblastoma cells

    2019, European Journal of Cell Biology
    Citation Excerpt :

    Live-cell confocal imaging with lipophilic dye showed that these shed structures also retained the dye, an indication that the plasma membrane was still intact. A study published in 2004, observed and discussed a highly similar process with CD44 and Integrin β1-positive cell fragments shed from the trailing edge of melanoma cells embedded in a collagen matrix in vitro (Mayer et al., 2004). They reported that this process was Integrin β1-dependent and suggested that this represents a fundamental mechanism for cell detachment from adhesive substrates (Mayer et al., 2004).

  • Adaptive F-Actin Polymerization and Localized ATP Production Drive Basement Membrane Invasion in the Absence of MMPs

    2019, Developmental Cell
    Citation Excerpt :

    While examining AC morphology, we detected spherical membrane structures that wild-type animals never displayed (n > 100). ACs in MMP− animals often (∼30%, n > 100) formed bleb-like structures that are attached to the cell body as well as detached tethered cell fragments (Figure S3E; Mayer et al., 2004; Wolf et al., 2003). These structures never formed at the AC’s invasive front, were usually not in contact with the BM, and were never observed penetrating BM (n = 50 animals observed) (Figure S3F).

  • Cell migration-The role of integrin glycosylation

    2010, Biochimica et Biophysica Acta - General Subjects
View all citing articles on Scopus
View full text