The influence of platelets on the promotion of invasion by tumor cells and inhibition by antiplatelet agents.
OBJECTIVE
Using a chemoinvasion assay, we show that platelets promote invasiveness of 5 pancreatic adenocarcinoma cell lines.


METHODS
Gelatin zymography and Western blot analysis were performed to detect metalloproteinase-9 (MMP-9) secreted from tumor cells in the presence or absence of platelets. The effects of antiplatelet agents on the invasiveness of tumor cells and the secretion level of MMP-9 were evaluated.


RESULTS
The number of traversed tumor cells significantly increased when incubated with platelets compared without platelets in all cell lines. The MMP-9 band was detected in all tumor cell lines, and the intensity was obviously greater in conditions of incubation with platelets than without. In the experiment of antiplatelet agents effects, it was confirmed that invasiveness of tumor cells significantly decreased following incubation with cilostazol depending on the concentration in spite of the presence of platelets. The level of MMP-9 also significantly decreased in the ELISA analysis.


CONCLUSIONS
These data mean platelets activate invasiveness of tumor cells because of enhanced MMP-9 secretion. Furthermore, anti-platelet drugs may inhibit invasiveness of tumor cells due to decreased MMP-9 secretion, and this inhibition may lead to the suppression of tumor cell invasion. We propose that antiplatelet agents are applicable in clinical treatment to inhibit metastasis of malignant tumor cells.
Suzuki
Keiichi
K
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Aiura
Koichi
K
Ueda
Masakazu
M
Kitajima
Masaki
M
D000230:Adenocarcinoma / Q000473:pathology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D045744:Cell Line, Tumor / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000077407:Cilostazol; D003094:Collagen; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D006801:Humans; D007797:Laminin; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000473:pathology*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011509:Proteoglycans; D013777:Tetrazoles / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D004338:Drug Combinations; D006629:Hirudins; D007797:Laminin; D009363:Neoplasm Proteins; D010975:Platelet Aggregation Inhibitors; D011509:Proteoglycans; D013777:Tetrazoles; C059485:matrigel; D000244:Adenosine Diphosphate; D003094:Collagen; D015118:Eicosapentaenoic Acid; D011464:Epoprostenol; D013917:Thrombin; D020780:Matrix Metalloproteinase 9; D000077407:Cilostazol