Invasiveness and MMP expression in pancreatic carcinoma.
BACKGROUND
Previous investigations have suggested that expression of matrix metalloproteinases (MMPs) may be related to increased invasiveness of various tumors. This study evaluated a possible relation between pancreatic tumor cell invasiveness and MMPs.


METHODS
A Matrigel invasion assay was performed with pancreatic tumor cell line SUIT-2 and its sublines S2-007, S2-013, S2-020, and S2-028. The degree of invasiveness of stimulated and unstimulated cell lines was correlated with MMP gene expression measured by RT-PCR and MMP protein product measured by gelatin zymography. Cell lines were stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), concanavalin (Con-A), and polymerized collagen type I gel (Vitrogen).


RESULTS
For SUIT-2, S2-007, S2-013, S2-020, and S2-028, 3.2, 1.0, 4.1, 6.4, and 0.4%, respectively, of the cells invaded the Matrigel membrane. TPA, Con-A, and Vitrogen resulted in the up-regulation of MMP-2 in S2-020. TPA and Vitrogen resulted in up-regulation of MMP-9 in each of the cell lines, while Con-A could up-regulate MMP-9 expression only in SUIT-2. There was no constitutive expression of either MMP-2 or MMP-9 in SUIT-2 or its sublines. There was a positive relationship between Matrigel invasiveness and up-regulation of MMP-2 and MMP-9 expression.


CONCLUSIONS
These data suggest that, while MMP-2 and MMP-9 are not constitutively expressed in pancreatic carcinoma cell lines, they may be up-regulated by TPA, Con-A, and Vitrogen. Since MMP-2 and MMP-9 expression correlated with degree of tumor cell invasiveness, the ability to up-regulate MMP-2 and MMP-9 expression may play a role in facilitating pancreatic tumor cell invasion.
Yang
X
X
Department of Surgery, Medical College of Ohio, Toledo, Ohio 43614-5807, USA.
Staren
E D
ED
Howard
J M
JM
Iwamura
T
T
Bartsch
J E
JE
Appert
H E
HE
D001672:Biocompatible Materials; D002277:Carcinoma / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix; D005782:Gels; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007797:Laminin; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011509:Proteoglycans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D014407:Tumor Cells, Cultured
D001672:Biocompatible Materials; D004338:Drug Combinations; D005782:Gels; D007797:Laminin; D011509:Proteoglycans; D019714:Tissue Inhibitor of Metalloproteinases; C093679:Vitrogen; D003208:Concanavalin A; C059485:matrigel; D003094:Collagen; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate