Inhibition of hyaluronan export attenuates cell migration and metastasis of human melanoma.
When secreted from malignant cells, hyaluronan facilitates tumor invasion and metastasis, as inhibition of its export by zaprinast inhibited metastasis formation in mice. However, the precise steps of the metastatic cascade, which were influenced by zaprinast, have not been identified as yet. Here we analyzed the cell biological effects of the inhibitor on three human melanoma cell lines that differed in their hyaluronan production and their metastatic capability when xenografted into SCID mice. We measured the influence of zaprinast on cellular hyaluronan export, surface coat formation, proliferation, random migration, colony formation in soft agar, adhesion, and transepithelial resistance. Concentrations of zaprinast not affecting cell proliferation, adhesion and transepithelial resistance, nevertheless reduced hyaluronan export by 50%, surface coat formation, random migration, and colony formation in soft agar. These results indicate that hyaluronan enhances metastasis formation primarily in those steps of the metastatic cascade, which involves tumor cell migration.
Monz
Katharina
K
Muenster University Hospital, Institute of Physiological Chemistry and Pathobiochemistry, Waldeyerstrasse 15, D-48129 Muenster, Germany.
Maas-Kück
Kathrin
K
Schumacher
Udo
U
Schulz
Tobias
T
Hallmann
Rupert
R
Schnäker
Eva Maria
EM
Schneider
Stefan W
SW
Prehm
Peter
P
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D008545:Melanoma / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011688:Purinones / Q000494:pharmacology
D011688:Purinones; D006820:Hyaluronic Acid; C011145:zaprinast