Gap junction proliferation in retinoic acid-treated human basal cell carcinoma
Elias, P.M.; Grayson, S.; Caldwell, T.M.; Mcnutt, N.S.
Laboratory Investigation; a Journal of Technical Methods and Pathology 42(4): 469-474
1980
ISSN/ISBN: 0023-6837 PMID: 7374110 Document Number: 164181
Retinoids are apparently potent antineoplastic agents, although the mechanisms of their action are unknown. In some cases, retinoids may act by maintaining epithelial differentiation. Because of the alleged importance of gap junctions in intercellular communication and growth control, and because a reduction in hemidesmosomes is a documented phenotypic basement membrane abnormality in basal cell carcinoma, the possibility that retinoids affect these structures in human basal cell carcinomas was tested. Fourteen previously untreated basal cell carcinomas were biopsied, allowed to heal for 1 wk, treated twice daily for 1 wk with 1% retinoic acid (RA) or vehicle control, and then surgically removed. Thin sections and freeze-fracture replicas of pretreated and posttreated samples were examined and photographed in a single-blind fashion; the density and size distribution of membrane structures were determined by planimetry. RA-treated samples demonstrated a greater than 2-fold increase in gap junction area per .mu.m2 of total membrane, vehicle controls demonstrated no significant change. This RA effect was primarily due to an increase in the number of junctions since the mean area of all gap junctions in RA-treated basal cell carcinoma showed no significant increase. The selectivity of the RA effect on gap junctions was underscored by a concurrent .simeq. 35% decrease in desmonsome density in RA-treated carcinomas; these changes could not be explained by cell volume alterations which remained unchanged. No significant qualitative changes were observed in hemidesmosomes or microfilaments at the epithelial-stromal interface. The observed increase in gap junction density probably represents an early event induced by retinoids that may relate to the antineoplastic activity of these compounds.