Expression of KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma and its potential involvement in tumor cell adhesion and invasion.
OBJECTIVE
Aberrant expressions of KL-6 mucin were proved to be associated with worse tumor behaviors of many carcinomas. This study was to evaluate the expression KL-6 mucin, a human MUC1 mucin, in intrahepatic cholangiocarcinoma (CC) and its significance in tumor progression.


METHODS
KL-6 mucin expressions in 21 patients with CC, 12 with combined hepatocellular and cholangiocarcinoma (cHCC-CC), and 78 with hepatocellular carcinoma (HCC) were detected by immunohistochemical staining. The effects of two glycosylation inhibitors (tunicamycin and benzyl-alpha-N-acetylgalactosamine (BAG)) on CC cell proliferations were assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assays. KL-6 mucin expressions were detected by immunocytochemical staining and western blotting after tunicamycin or BAG treatment. Cell adhesive and invasive properties were evaluated by adhesion tests and transwell chamber assays after tunicamycin or BAG treatment.


RESULTS
Positive KL-6 mucin staining was observed in all CC tissues and CC areas of cHCC-CC tissues. Immunocytochemical staining and western blotting showed that KL-6 mucin expressions were significantly reduced after both inhibitors treatment. Cell adhesive properties were significantly decreased after both inhibitors treatment, while cell invasive abilities were significantly decreased after BAG but not tunicamycin treatment.


CONCLUSIONS
This study indicated that KL-6 mucin might be a specific tumor target for CC. Therapeutic strategies that target glycosylation of KL-6 mucin may be useful to control aggressive behaviors of CC.
Xu
H L
HL
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo 113-8655, Japan.
Inagaki
Y
Y
Seyama
Y
Y
Sugawara
Y
Y
Kokudo
N
N
Nakata
M
M
Wang
F S
FS
Tang
W
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000503:physiopathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology; D055815:Young Adult
D000900:Anti-Bacterial Agents; C060192:MUC1 protein, human; D018396:Mucin-1; D014415:Tunicamycin