Release of Cell Fragments by Invading Melanoma Cells

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, beta1 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 microm in diameter, contain cytoplasm and occasionally polymerized actin enclosed by intact cell membrane including surface beta1 integrins, but do not include nuclear material. The release of cell fragments was migration dependent, as impairment of motility by a blocking anti-beta1 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.