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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 4/2014

01-12-2014 | Translational Research and Biomarkers

CEACAM1 Long Cytoplasmic Domain Isoform is Associated with Invasion and Recurrence of Hepatocellular Carcinoma

Authors: Shigehisa Kiriyama, MD, Shozo Yokoyama, MD, PhD, Masaki Ueno, MD, PhD, Shinya Hayami, MD, PhD, Junji Ieda, MD, PhD, Naoyuki Yamamoto, MD, Shunsuke Yamaguchi, MD, Yasuyuki Mitani, MD, Yasushi Nakamura, MD, PhD, Masaji Tani, MD, PhD, Lopa Mishra, MD, John E. Shively, PhD, Hiroki Yamaue, MD, PhD

Published in: Annals of Surgical Oncology | Special Issue 4/2014

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Abstract

Background

The two isoforms of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), 1 with a long cytoplasmic domain (CEACAM1-L) and 1 with a short (CEACAM1-S), are involved in different signaling pathways. β2-spectrin (β2SP) is an adaptor protein that plays critical roles in the proper control of Smad access to activate receptors involved in regulation of TGF-β signaling. In this study, we examined the association between CEACAM1 isoform balance and hepatocellular carcinoma (HCC) malignant potential and investigated the possibility of a molecular interaction between CEACAM1 and β2SP.

Methods

Immunohistochemical analysis was carried out with CEACAM1-L or CEACAM1-S antibodies on 154 HCC tissues to correlate with the factors of malignancy. Invasion assay was performed for the effect of CEACAM1 expression on HCC cell lines. Moreover, immunohistochemical analysis and immunoprecipitation analysis were performed to investigate the association between CEACAM1 isoform balance and β2SP.

Results

In immunohistochemical analysis, CEACAM1-L expression dominance was a risk factor for HCC recurrence (p = 0.04) and was significantly associated with a shorter survival compared with CEACAM1-S expression dominance. Invasion assay indicated that CEACAM1-4L-transfected HLF and PLC/PRF/5 cells showed significantly increased invasion (p < 0.0001) and CEACAM1-4S-transfected HLF cells showed significantly decreased invasion. Immunohistochemical analysis of β2SP suggested that the HCCs with CEACAM1-L-dominant expression were more strongly stained with β2SP than the HCCs with CEACAM1-S-dominant expression (p = 0.013), and coprecipitation assays indicated that CEACAM1-L could bind to β2SP.

Conclusions

CEACAM1-L may enhance the HCC invasiveness through an interaction with β2SP and subsequent effects on TGF-β signaling.
Appendix
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Metadata
Title
CEACAM1 Long Cytoplasmic Domain Isoform is Associated with Invasion and Recurrence of Hepatocellular Carcinoma
Authors
Shigehisa Kiriyama, MD
Shozo Yokoyama, MD, PhD
Masaki Ueno, MD, PhD
Shinya Hayami, MD, PhD
Junji Ieda, MD, PhD
Naoyuki Yamamoto, MD
Shunsuke Yamaguchi, MD
Yasuyuki Mitani, MD
Yasushi Nakamura, MD, PhD
Masaji Tani, MD, PhD
Lopa Mishra, MD
John E. Shively, PhD
Hiroki Yamaue, MD, PhD
Publication date
01-12-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue Special Issue 4/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3460-1

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