Suppression of metastatic potential of high-metastatic Lewis lung carcinoma cells by vanadate, an inhibitor of tyrosine phosphatase, through inhibiting cell-substrate adhesion.
Treatment of high-metastatic Lewis lung carcinoma A11 cells with sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, resulted in a dose- and time-dependent suppression of cell spreading on various extracellular matrix components such as Matrigel, fibronectin, laminin and type IV collagen, while the treatment did not significantly inhibit attachment of the cells to these substrates. Orthovanadate slightly and reversibly inhibited the in vitro cell growth of A11 cells, but the suppression of cell spreading was not directly due to the inhibition of cell growth. Orthovanadate-treated A11 cells showed reduced invasive ability in a reconstituted basement membrane invasion assay and experimental metastatic ability. Protein tyrosine phosphorylation level in A11 cells was elevated after treatment with orthovanadate. The increase in tyrosine phosphorylation level was partially diminished by the tyrosine kinase inhibitor ST638, concomitantly with restoration of the suppressed cell spreading as well as invasive and metastatic abilities. These results suggest that protein tyrosine phosphorylation influences invasive and metastatic potential of tumor cells possibly through regulating cell-substrate adhesion.
Takenaga
K
K
Division of Chemotherapy, Chiba Cancer Center Research Institute, Japan.
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use; D003094:Collagen; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007797:Laminin; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011509:Proteoglycans; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002934:Cinnamates; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D007797:Laminin; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011509:Proteoglycans; D013440:Sulfides; C060747:ST 638; C059485:matrigel; D014638:Vanadates; D003094:Collagen; D017027:Protein Tyrosine Phosphatases