Pancreatic cancer stem cell markers and exosomes - the incentive push

Figure 6 Contribution of exosomal cancer stem cell markers to target selection, binding, uptake and target modulation. A: Exosomes uptake by cells can proceed via membrane fusion, macropinocytosis, receptor ligand binding. GEM-derived exosomes bind to complexes of ligands located in internalization prone membrane microdomains, which increases selectivity of uptake and facilitates uptake; B: Binding to the ECM is facilitated by the Pa-CSC markers α6β4 and CD44v6. CD44v6- and Tspan8-associated proteases facilitate matrix degradation; C-E: There are multiple pathways whereby TEX affect target cells, only selected examples are shown: Signal transduction can be initiated by clustering GEM ligands; in progenitor cells, e.g., in the bone marrow, activation of signaling molecules can initiate a shift towards differentiation; the transfer of TEX miRNA can initiate release from repression by the miRNA target or tumor suppressor RNA can become silenced such that resting mesenchymal cells turn into an activated phenotype; F: EMT was induced in Non-CSC by the transfer of oncogenes, activation of EMT-related transcription factors or miRNA blocking transcription of RNA engaged in epithelial stage maintenance. CSC: Cancer stem cells; GEM: Glycolipid-enriched microdomains; ECM: Extracellular matrix; EMT: Epithelial mesenchymal transition; HA: Hyaluronan; TEX: Tumor exosomes.