Retinoic Acid Differentiation of HL-60 Cells Promotes Cytoskeletal Polarization

• Published in: Experimental cell research Vol. 254; no. 1; pp. 130 - 142
• Main Authors: Olins, Ada L., Herrmann, Harald, Lichter, Peter, Olins, Donald E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.01.2000
• Subjects: Actins - metabolism; Animals; Apoptosis; Cell Differentiation; Cell Nucleus - drug effects; Centrosome - drug effects; Centrosome - metabolism; centrosome microtubules; Cytochalasin D - pharmacology; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Cytoskeleton - physiology; granulocytes; HL-60 Cells - cytology; Humans; Interphase - drug effects; Mice; Microtubules - drug effects; Microtubules - metabolism; nuclear envelope; Paclitaxel - pharmacology; retinoic acid; Tretinoin - pharmacology; Tubulin - metabolism; Vimentin - metabolism; granulocytes; nuclear envelope; retinoic acid; centrosome microtubules
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.1999.4727

Retinoic acid (RA) treatment of HL-60 cells in vitro induces granulocytic differentiation, involving reorganization of the nucleus and cytoplasm, development of chemoattractant-directed migration, and eventual apoptosis. The present studies with HL-60/S4 cells document that major elements of the cytoskeleton are changed: actin increases by 50%; vimentin decreases by more than 95%. The cellular content of α-tubulin does not significantly change; but the centrosomal–microtubule (MT) array moves away from the lobulating nucleus. Cytoskeletal-modifying chemicals modulate this polarized reorganization: Taxol and cytochalasin D enhance centrosome movement; nocodazole reverses it. Cytoskeletal-modifying chemicals do not appear to affect nuclear lobulation or the integrity of envelope-limited chromatin sheets (ELCS). Employing bcl-2-overexpressing HL-60 cells permitted demonstration of nuclear lobulation, ELCS formation, and centrosome–MT movement concomitantly during RA-induced differentiation, implying independence between the cellular reorganization and apoptotic programs. RA appears to promote an inherent potential in HL-60 cells for cytoskeletal polarization, likely to be important for chemoattractant-directed cell migration, an established characteristic of mature granulocytes.