Adhesion and Signaling of Tumor Cells to Leukocytes and Endothelium in Cancer Metastasis

摘要: Heterotypic cell–cell adhesion in the near wall region under dynamic shear forces has been studied. In particular, we focus on neutrophil (PMN)–melanoma cell emboli formation a non-linear flow and subsequent tethering to vascular endothelium (EC) as result of aggregation. The extent tumor vessel is governed by kinetic formation/disruption receptor–ligand bonds, soluble signaling proteins within microenvironment, hydrodynamic circulation. Upon arrest endothelium, retraction EC during extravasation occurs due disruption intercellular channels or disassembly endothelial (VE)-cadherin homodimers that allow passage cells. Preliminary studies have found tumor-elicited PMNs increase melanoma extravasation, which involves subsequently capturing/maintaining cells close proximity EC. Results indicated novel finding PMN-facilitated mediated binding between molecule (ICAM)-1 (expressing both ECs) β2 integrins PMNs, influenced tumor-induced inflammatory cytokines, e.g., interleukin (IL)-8, rates. Furthermore, adherens junctions terms VE-cadherin are regulated mitogen activated protein kinases (MAPK) response EC, well IL-8 several other microenvironment. These will yield new evidence for complex role hemodynamics, signaling, heterotypic recruitment metastatic cancer microcirculation metastasis, be significant fostering cross-disciplinary approaches treatment.