Influence of topical and systemic retinoids on basal cell carcinoma cell membranes.
Although much recent work suggests that retinoids can prevent the development of epithelial cancers, their mechanism of action remains unknown. Since malignancy has been associated with alterations in gap junctions, desmosomes, microfilaments, and hemidesmosomes, the authors examined freeze-fracture replicas and thin sections of cell membranes of: (1) 11 basal cell cancers (BCC) treated twice daily for two weeks with topical 1.0% retinoid acid (RA); (2) 21 BCC treated for 2 to 17 weeks with oral 13-cis retinoic acid (CRA) (1.0-8.0 mg/kg/day); and (3) 17 BCC prior to retinoid treatment and/or after applications of vehicle alone. Both thin sections and replicas were examined and photographed in a single-blind fashion, and the density and size distribution of gap junctions and desmosomes were computed planimetrically. Topical RA treatment induced a two-fold increase in gap junction density (P less than 0.025) over controls. In contrast, RA produced a concurrent = 35% decrease in desmosome density. Systemic CRA did not significantly alter either gap junction or desmosome density or size. Finally, neither RA nor CRA treatment appeared to influence hemidesmosome or microfilament populations. Structural changes in both treatment groups did not correlate with either tumor regression or inflammation. Topical and systemic retinoids may exert their antineoplastic activity by different cellular mechanisms.
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D003896:Desmosomes / Q000187:drug effects / Q000648:ultrastructure; D005614:Freeze Fracturing; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D014212:Tretinoin / Q000008:administration & dosage; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives*
D014801:Vitamin A; D014212:Tretinoin