A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells

4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decrease...

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Bibliographic Details
Published in:FEBS letters 2005-05, Vol.579 (12), p.2722-2726
Main Authors: Yoshihara, Shuichi, Kon, Atsushi, Kudo, Daisuke, Nakazawa, Hideaki, Kakizaki, Ikuko, Sasaki, Mutsuo, Endo, Masahiko, Takagaki, Keiichi
Format: Article
Language:English
Subjects:
4-Methylumbelliferone
Administration, Oral
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - blood
Antineoplastic Agents - pharmacology
Cell Adhesion - drug effects
Cell Movement - drug effects
FCS
Female
fetal calf serum
GAG
Glucuronosyltransferase - antagonists & inhibitors
glycosaminoglycan
HAS
Hyaluronan
hyaluronan synthase
Hyaluronan Synthases
Hymecromone - administration & dosage
Hymecromone - analogs & derivatives
Hymecromone - blood
Hymecromone - pharmacology
Liver
Liver Neoplasms - secondary
Melanoma cell
Melanoma, Experimental - drug therapy
Melanoma, Experimental - pathology
Melanoma, Experimental - physiopathology
Metastasis
Mice
Mice, Inbred C57BL
Neoplasm Metastasis - prevention & control
PBS
phosphate-buffered saline
UDP-glucuronosyltransferase
UGT
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Description
Summary:4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation, and that such inhibition results in suppression of adhesion and locomotion of cultured melanoma cells. Here, we examine the effect of MU on melanoma cell metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface HA formation and suppression of liver metastasis after injection into the mice. Oral administration of MU to mice decreased tissue HA content. These HA knock-down mice displayed suppressed liver metastasis. Thus, both cell surface HA of melanoma cells and recipient liver HA can promote liver metastasis, indicating that MU has potential as an anti-metastatic agent.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2005.03.079