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

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

doi:10.1245/s10434-013-3460-1

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

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

Gastroenterology Hepatology & Nutrition

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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.

Original language	English (US)
Pages (from-to)	505-514
Number of pages	10
Journal	Annals of surgical oncology
Volume	21
Issue number	4
DOIs	https://doi.org/10.1245/s10434-013-3460-1
State	Published - 2014

ASJC Scopus subject areas

Surgery
Oncology

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10.1245/s10434-013-3460-1

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Kiriyama, S., Yokoyama, S., Ueno, M., Hayami, S., Ieda, J., Yamamoto, N., Yamaguchi, S., Mitani, Y., Nakamura, Y., Tani, M., Mishra, L., Shively, J. E., & Yamaue, H. (2014). CEACAM1 Long Cytoplasmic Domain Isoform is Associated with Invasion and Recurrence of Hepatocellular Carcinoma. Annals of surgical oncology, 21(4), 505-514. https://doi.org/10.1245/s10434-013-3460-1

@article{024a26bcddf843409c98fa6ef60506de,

title = "CEACAM1 Long Cytoplasmic Domain Isoform is Associated with Invasion and Recurrence of Hepatocellular Carcinoma",

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.",

author = "Shigehisa Kiriyama and Shozo Yokoyama and Masaki Ueno and Shinya Hayami and Junji Ieda and Naoyuki Yamamoto and Shunsuke Yamaguchi and Yasuyuki Mitani and Yasushi Nakamura and Masaji Tani and Lopa Mishra and Shively, {John E.} and Hiroki Yamaue",

note = "Funding Information: Grant-in-Aid No. 20591554 and 23591904 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and Takeda Science Foundation, Japan. Publisher Copyright: {\textcopyright} 2014, Society of Surgical Oncology.",

year = "2014",

doi = "10.1245/s10434-013-3460-1",

language = "English (US)",

volume = "21",

pages = "505--514",

journal = "Annals of surgical oncology",

issn = "1068-9265",

publisher = "Springer New York",

number = "4",

}

TY - JOUR

T1 - CEACAM1 Long Cytoplasmic Domain Isoform is Associated with Invasion and Recurrence of Hepatocellular Carcinoma

AU - Kiriyama, Shigehisa

AU - Yokoyama, Shozo

AU - Ueno, Masaki

AU - Hayami, Shinya

AU - Ieda, Junji

AU - Yamamoto, Naoyuki

AU - Yamaguchi, Shunsuke

AU - Mitani, Yasuyuki

AU - Nakamura, Yasushi

AU - Tani, Masaji

AU - Mishra, Lopa

AU - Shively, John E.

AU - Yamaue, Hiroki

N1 - Funding Information: Grant-in-Aid No. 20591554 and 23591904 from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and Takeda Science Foundation, Japan. Publisher Copyright: © 2014, Society of Surgical Oncology.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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U2 - 10.1245/s10434-013-3460-1

DO - 10.1245/s10434-013-3460-1

M3 - Article

C2 - 24390710

AN - SCOPUS:84891435142

SN - 1068-9265

VL - 21

SP - 505

EP - 514

JO - Annals of surgical oncology

JF - Annals of surgical oncology

IS - 4

ER -

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

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