Retinoic acid differentiation of HL-60 cells promotes cytoskeletal polarization.
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 alpha-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.
Olins
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Foundation for Blood Research, 69 US Route One, Scarborough, Maine, 04070-0190, USA.
Herrmann
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Lichter
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Olins
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D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000187:drug effects; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018922:HL-60 Cells / Q000166:cytology; D006801:Humans; D007399:Interphase / Q000187:drug effects; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D014404:Tubulin; D014746:Vimentin; D015638:Cytochalasin D; D014212:Tretinoin; D017239:Paclitaxel