Induction of reversible changes in cell-surface glycoconjugates and lung colonization potential by 13-cis retinoic acid.
Murine squamous carcinoma cells (KLN205) grown in a medium supplemented with the retinoid, 13-cis retinoic acid (RA), had dose-dependent, selective increases in the expression of certain lectin receptors, which correlated with a dramatic decrease in the ability to form pulmonary colonies (P = .0003) (Couch MJ, Pauli BU, Weinstein RS, Coon JS: JNCI, 78:971-977, 1987). These findings suggest a possible relationship between the RA-induced glycoconjugate alterations and the decreased experimental metastatic behavior. We further define the mechanism of RA's action. The finding that RA treatment (5 X 10(-6) M, 5 X 10(-7) M) did not perturb the cell cycle of KLN205 cells provides further proof that the decreased metastatic behavior is not attributable to any inhibition in the rate of growth or to alterations in the cell cycle. Furthermore, since stable subpopulations with variable lectin binding could not be detected, the mechanism of RA's action does not appear to be due to selection of variant tumor-cell subpopulations. Finally, in a series of experiments designed to determine the reversibility of the RA treatment, the RA-induced decrease in metastatic behavior reverted back to a more metastatic state in the same time frame (3 days) as the reversion of the RA-induced changes in cell-surface glycoconjugate expression. This reversion provides further evidence for a close relationship between the RA-induced modulation of tumor cell-surface glycoconjugate expression and the decreased metastatic behavior; it suggests that transient, reversible modulation of the tumor cell surface may play a role in determining metastatic behavior.
Couch
M J
MJ
Department of Immunology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Pauli
B U
BU
Weinstein
R S
RS
Coon
J S
JS
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D002453:Cell Cycle / Q000187:drug effects; D005434:Flow Cytometry; D006001:Glycoconjugates / Q000378:metabolism*; D015474:Isotretinoin; D037102:Lectins / Q000378:metabolism; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D009362:Neoplasm Metastasis; D011975:Receptors, Mitogen / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006001:Glycoconjugates; D037102:Lectins; D011975:Receptors, Mitogen; D014212:Tretinoin; D015474:Isotretinoin