title: Suppression of melanoma cell motility factor receptor expression by retinoic acid.
abstract: beta-All-trans-retinoic acid (RA) has been shown to inhibit the growth, enhance the differentiation, and suppress the transformed and metastatic properties of certain human and murine melanoma cells. This study examined the effect of RA on the level of a cell surface receptor (M(r) 78,000) (gp78) for an autocrine motility factor, which has been implicated in invasion and metastasis. Treatment of murine melanoma cell lines S91-C2, B16-F1, and K1735-P with RA (10 microM) for 5 days decreased the level of gp78 by 37, 72, and 92%, respectively, as revealed by immunoblotting with monoclonal antibodies raised against gp78. In contrast, RA had only a limited effect on gp78 levels in melanoma cell clones or variant cell lines that are resistant to the growth-inhibitory effects of RA (S91-C154, B16-F10, and K1735-Cl19). Further studies with K1735-P, the most sensitive cell line with respect to modulation of gp78, showed that the decrease in gp78 level required at least 1 microM RA and 4 to 5 days of treatment. The binding of anti-gp78 antibodies to the surface of intact RA-treated cells and to intracellular gp78 in permeabilized cells was also lower than in untreated cells. Furthermore, RA treatment decreased the induction of cell motility, on colloidal gold-coated glass coverslips, by anti-gp78 antibodies, which mimic the effect of autocrine motility factor. The RA-induced decrease in antibody-enhanced cell motility was similar to the time- and RA concentration-dependent decrease in the amount of gp78, suggesting that the two events are related. These results raise the possibility that the previously reported suppression by RA of tumor cell invasion and metastasis may be related, at least in part, to suppression of cell motility resulting from the decreased level of the autocrine motility factor receptor.
authors.affiliation: Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: R
authors.initials: R
authors.lastname: Lotan
authors.forename: B
authors.initials: B
authors.lastname: Amos
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Raz
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism*; D066298:In Vitro Techniques; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D060285:Receptors, Autocrine Motility Factor; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018121:Receptors, Cytokine; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
chemical_list: D000911:Antibodies, Monoclonal; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D014212:Tretinoin; C555000:AMFR protein, human; C555002:Amfr protein, mouse; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D005956:Glucose-6-Phosphate Isomerase