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Inhibition of hyaluronan export attenuates cell migration and metastasis of human melanoma
Author(s) -
Monz Katharina,
MaasKück Kathrin,
Schumacher Udo,
Schulz Tobias,
Hallmann Rupert,
Schnäker Eva Maria,
Schneider Stefan W.,
Prehm Peter
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21925
Subject(s) - zaprinast , cell migration , metastasis , hyaluronic acid , cancer research , chemistry , cell adhesion , cell , cell growth , melanoma , cell culture , adhesion , microbiology and biotechnology , biology , medicine , biochemistry , cancer , phosphodiesterase , anatomy , enzyme , genetics , organic chemistry
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. J. Cell. Biochem. 105: 1260–1266, 2008. © 2008 Wiley‐Liss, Inc.