title: Co-expression of matriptase and N-acetylglucosaminyltransferase V in thyroid cancer tissues--its possible role in prolonged stability in vivo by aberrant glycosylation.
abstract: UDP-N-acetylglucosamine:alpha-mannoside beta-1,6-N-acetylglucosaminyltransferase (GnT-V) catalyzes the formation of beta-1-6 GlcNAc branches on asparagine-linked oligosaccharides, which is directly linked to tumorigenesis. Our recent studies indicate that the secretion of matriptase from cancer cells is increased via the action of GnT-V, as evidenced by the fact that matriptase-bearing beta-1-6 GlcNAc branching is dramatically inhibited. In this study, we report on an investigation of the expression of GnT-V and matriptase in thyroid neoplasm tissues to determine the clinical significance on the co-expression of these two proteins in thyroid cancer. Although neither GnT-V nor matriptase was expressed in normal thyroid tissue, positive staining for matriptase and GnT-V was observed in 52/68 and 66/68 cases of papillary carcinoma, 3/23 and 10/23 cases of follicular carcinoma, 5/13 and 9/13 cases of follicular adenoma, and 11/28 and 6/28 cases of anaplastic carcinoma, respectively. Immunohistochemistry, as well as western blotting, showed that the expression of matriptase paralleled the expression to GnT-V. However, the expression of matriptase mRNA was not correlated with its protein levels, suggesting that the enhancement in matriptase expression could be regulated by a posttranslational modification such as glycosylation through GnT-V-mediated glycosylation. In papillary carcinoma, the levels of expression of both GnT-V and matriptase were significantly higher in tumors 1 cm or less in size (microcarcinoma) and in those without poorly differentiated lesions, and the two proteins were significantly correlated. In contrast, the prognosis of thyroid carcinoma after surgery was neither correlated with the expression GnT-V nor matriptase, because the levels of their expression were quite low in anaplastic (undifferentiated) carcinomas. These results suggest that prolonged stabilization of matriptase is stabilized by GnT-V-mediated glycosylation in vivo, thus extending its halftime and permitting it to play role in the early phases of papillary carcinoma, but not in its later phase progression.
authors.affiliation: Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku. Kobe 650-0011, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Ayumi
authors.initials: A
authors.lastname: Akinaga
authors.forename: Kanako
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kondo
authors.forename: Robert B
authors.initials: RB
authors.lastname: Dickson
authors.forename: Chen-Yong
authors.initials: CY
authors.lastname: Lin
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
mesh_terms: D015153:Blotting, Western; D004795:Enzyme Stability; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000145:classification* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; D012697:Serine Endopeptidases; C485595:matriptase