Oncotarget

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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

Sae Won Kim, Hyun Gul Yang, Moon Cheol Kang, Seungwon Lee, Hong Namkoong, Seung-Woo Lee and Young Chul Sung _

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Oncotarget. 2014; 5:1226-1240. https://doi.org/10.18632/oncotarget.1677

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Abstract

Sae Won Kim1, Hyun Gul Yang2, Moon Cheol Kang2, Seungwon Lee2, Hong Namkoong1, Seung-Woo Lee1, 2, Young Chul Sung1, 2

1 Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea

2 Integrative Biosciences & Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk, Republic of Korea

Correspondence:

Dr. Young Chul Sung, e-mail: ycsung@postech.ac.kr

Dr. Seung-Woo Lee, e-mail: sw_lee@postech.ac.kr

Key Words: Tumor-initiating cells, hepatocellular carcinoma, KIAA1114, cell surface marker, monoclonal antibody

Received: December 10, 2013      Accepted: March 20, 2014     Published: March 31, 2014

ABSTRACT

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.


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