TPA-enhanced invasion of Matrigel associated with augmentation of cell motility but not metalloproteinase activity in a highly metastatic variant (L-10) of human rectal adenocarcinoma cell line RCM-1.
We previously found that the enhanced activity to invade Matrigel upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) was one of the major properties of a highly metastatic variant (L-10) of a human rectal adenocarcinoma cell line RCM-1. To clarify the mechanism of this enhancement, we examined the effect of TPA on 2 major biological factors involved in tumor cell invasion: cell motility and matrix-degrading metalloproteinase activity. The enhanced invasiveness was inhibited by protein-kinase-C inhibitors. TPA markedly enhanced both haptotactic response to type-IV collagen and motility on tissue-culture glass substrate of L-10 cells in a dose-response manner quite similar to that of TPA-enhanced invasion of Matrigel. On the other hand, TPA showed little enhancement of metalloproteinase production, which was assessed by gelatin- and casein-zymography, and of type-IV collagenolytic activity. Addition of TIMP (tissue inhibitors of metalloproteinase)-I inhibited TPA-enhanced invasion of Matrigel by only up to 13%. Thus, TPA treatment of L-10 cells enhanced invasion of Matrigel in association with augmentation of cell motility but did not enhance metalloproteinase activity.
Nabeshima
K
K
Department of Pathology, Miyazaki Medical College, Japan.
Komada
N
N
Kishi
J
J
Koita
H
H
Inoue
T
T
Hayakawa
T
T
Koono
M
M
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology*; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen; D004338:Drug Combinations; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D007797:Laminin; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011509:Proteoglycans; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000470:Alkaloids; D004338:Drug Combinations; D006023:Glycoproteins; D007797:Laminin; D011509:Proteoglycans; D019714:Tissue Inhibitor of Metalloproteinases; D010566:Virulence Factors, Bordetella; C059485:matrigel; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003094:Collagen; D011493:Protein Kinase C; D008666:Metalloendopeptidases; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate