Modulation of the metastatic phenotype by 13-cis-retinoic acid.
KLN 205 murine squamous carcinoma cells were grown in medium supplemented with the retinoid 13-cis-retinoic acid (RA) to study the relationship between RA-induced cell surface changes and alterations of the metastatic phenotype. Modulation of the cell surface glycoconjugate expression was measured by flow cytometric analysis of the RA-treated tumor cells stained with fluoresceinated lectins. RA treatment (5 X 10(-6) and 5 X 10(-7) M) altered the glycoconjugate expression of KLN 205 cells in a selective, dose-dependent fashion. Tumor cells grown in RA-supplemented medium for more than 4 days demonstrated greatly increased binding of fluoresceinated Griffonia simplicifolia I lectin, peanut lectin, wheat-germ lectin, concanavalin A, and soybean lectin (P less than .001), but the increased binding of Ulex europaeus lectin was of a much smaller magnitude (P = .02). After 15 days of growth in these noncytotoxic or cytostatic concentrations of RA, malignant KLN 205 cells had a greatly decreased proclivity to metastasize, as measured by the lung colony assay (P = .0003). The RA-induced cell surface glycoconjugate changes preceded the decrease in experimental metastatic potential. Since enzymatic (neuraminidase) alteration of the tumor cell surface to produce glycoconjugate expression similar to that seen in RA-treated cells also reduced the ability of the KLN 205 cells to form lung colonies (P = .0022), it is suggested that RA-induced alteration of the cell surface carbohydrate antigens is related to the decreased experimental metastatic potential seen in tumor cells treated with RA.
Couch
M J
MJ
Pauli
B U
BU
Weinstein
R S
RS
Coon
J S
JS
D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D002241:Carbohydrates / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005453:Fluorescence; D015474:Isotretinoin; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary; D008358:Mannose / Q000378:metabolism; D051379:Mice; D009362:Neoplasm Metastasis; D010641:Phenotype; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D002241:Carbohydrates; D014212:Tretinoin; D015474:Isotretinoin; D008358:Mannose