KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes.
Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen, KIAA1114, as a potential diagnostic factor of human liver cancer, but also as an independent biomarker for identifying TIC populations that could be broadly applied to the heterogeneous HCC subtypes.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea.
Sae Won
SW
Kim
Hyun Gul
HG
Yang
Moon Cheol
MC
Kang
Seungwon
S
Lee
Hong
H
Namkoong
Seung-Woo
SW
Lee
Young Chul
YC
Sung
D000818:Animals; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D018281:Cholangiocarcinoma / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018874:Spheroids, Cellular; D014410:Tumor Stem Cell Assay; D000509:alpha-Fetoproteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; C093649:TRO protein, human; D000509:alpha-Fetoproteins