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 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.
Yoshihara
Shuichi
S
Department of Surgery, Hirosaki University School of Medicine, Japan.
Kon
Atsushi
A
Kudo
Daisuke
D
Nakazawa
Hideaki
H
Kakizaki
Ikuko
I
Sasaki
Mutsuo
M
Endo
Masahiko
M
Takagaki
Keiichi
K
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D000076002:Hyaluronan Synthases; D006923:Hymecromone / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D008113:Liver Neoplasms / Q000556:secondary*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*
D000970:Antineoplastic Agents; D006923:Hymecromone; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases