All-trans-retinoic acid-dependent inhibition of E-cadherin-based cell adhesion with concomitant dephosphorylation of beta-catenin in metastatic human renal carcinoma cells.
We previously described an in vitro invasion assay model, using a monolayer of vascular endothelial cells grown on collagen gel, that mimics the metastatic abilities of the highly metastatic human renal carcinoma cell lines, MM-1,3 and 8 and their poorly metastatic counterparts, SN12C and Cl-8. MM-1, 3 and 8 cells were observed to penetrate the monolayer of vascular endothelial cells and grew in a spreading or scattering manner with loose cell-cell contact on collagen gel or on vascular endothelial cells. SN12C and Cl-8 cells failed to penetrate and grew in a clustering manner with tight cell-cell contact. Treatment with all-trans-retinoic acid (ATRA) at non-toxic concentrations induced clustering or growth of MM-1, 3 and 8 cells on collagen gel or on vascular endothelial cells with tight cell-cell contact, and inhibited penetration. The clustering induced by ATRA was virtually blocked in the presence of anti-E cadherin antibody. E-Cadherin and beta-catenin were each localized mainly at the cell-cell adherent junctions of colonizing cell populations that had been treated with ATRA. While the cellular levels of E-cadherin and beta-catenin did not change significantly following ATRA treatment, the tyrosine residue of beta-catenin was rapidly dephosphorylated. The concomitant administration of Na vanadate, an inhibitor of tyrosine dephosphorylase, inhibited both the ATRA-induced clustering and the dephosphorylation of beta-catenin tyrosine. ATRA-induced clustering of MM-3 cells may be linked to the state of tyrosine phosphorylation of beta-catenin.
Ryuto
M
M
Department of Otorhinolaryngology, Kyushu University School of Medicine, Fukuoka.
Jimi
S
S
Ono
M
M
Naito
S
S
Nakayama
Y
Y
Yamada
Y
Y
Komiyama
S
S
Kuwano
M
M
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D015820:Cadherins / Q000276:immunology / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000556:secondary; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D010766:Phosphorylation / Q000187:drug effects; D015534:Trans-Activators; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology; D051176:beta Catenin
D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin; D014638:Vanadates; D014212:Tretinoin