Volume 118, Issue 4 pp. 664-674

RESEARCH ARTICLE

CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

Ryoya Yamaoka MD,

Ryoya Yamaoka MD

orcid.org/0000-0003-4385-2425

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Takamichi Ishii MD, PhD,

Corresponding Author

Takamichi Ishii MD, PhD

[email protected]

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Correspondence Takamichi Ishii, MD, PhD, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Email: [email protected]

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Takayuki Kawai MD, PhD,

Takayuki Kawai MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Kentaro Yasuchika MD, PhD,

Kentaro Yasuchika MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Yuya Miyauchi MD,

Yuya Miyauchi MD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Hidenobu Kojima MD,

Hidenobu Kojima MD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Hokahiro Katayama MD, PhD,

Hokahiro Katayama MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Satoshi Ogiso MD, PhD,

Satoshi Ogiso MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Ken Fukumitsu MD, PhD,

Ken Fukumitsu MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Shinji Uemoto MD, PhD,

Shinji Uemoto MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Ryoya Yamaoka MD,

Ryoya Yamaoka MD

orcid.org/0000-0003-4385-2425

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Takamichi Ishii MD, PhD,

Corresponding Author

Takamichi Ishii MD, PhD

[email protected]

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Correspondence Takamichi Ishii, MD, PhD, Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Email: [email protected]

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Takayuki Kawai MD, PhD,

Takayuki Kawai MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Kentaro Yasuchika MD, PhD,

Kentaro Yasuchika MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Yuya Miyauchi MD,

Yuya Miyauchi MD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Hidenobu Kojima MD,

Hidenobu Kojima MD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Hokahiro Katayama MD, PhD,

Hokahiro Katayama MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Satoshi Ogiso MD, PhD,

Satoshi Ogiso MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Ken Fukumitsu MD, PhD,

Ken Fukumitsu MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Shinji Uemoto MD, PhD,

Shinji Uemoto MD, PhD

Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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First published: 09 September 2018

https://doi.org/10.1002/jso.25192

Citations: 14

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Abstract

Background and Objectives

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. However, its prognosis remains poor. Expression of cluster of differentiation 90 (CD90) has been identified as an indicator of poor prognosis in many cancers. Here, we examined the importance of CD90 expression in ICC.

Methods

We performed immunohistological assays for CD90 in human ICC surgical specimens and assessed its relationship with clinicopathological findings and prognosis. Moreover, we analyzed the characteristics of CD90^+/− cells, mainly with respect to metastatic potential, using human ICC cell lines.

Results

CD90 expression was significantly associated with lymph node metastasis and was revealed to be an independent prognostic factor. The CD90⁺ cells present in ICC specimens did not appear to be cancer-associated fibroblasts, as they did not express α-smooth muscle actin. In vitro, CD90 ⁺ cells exhibited greater migratory ability and higher expression of epithelial-mesenchymal transition (EMT)–related genes, including CXCR4 and MMP7, than CD90⁻ cells. Wnt/β-catenin signaling pathway activation was also heightened in CD90⁺ cells. In such cells, EMT appeared to be induced by CXCR4 and MMP7 expression through activation of Wnt/β-catenin signaling.

Conclusion

CD90⁺ cells demonstrate high metastatic potential owing to Wnt/β-catenin signaling activation and are associated with poor prognosis in ICC.

CONFLICTS OF INTEREST

All authors declare that there are no conflicts of interest.

Supporting Information

REFERENCES

1Gores G. Cholangiocarcinoma: current concepts and insights. Hepatology. 2003; 37: 961-969.
10.1053/jhep.2003.50200
PubMed Web of Science® Google Scholar
2Patel T. Cholangiocarcinoma – controversies and challenges. Nat Rev Gastroenterol Hepatol. 2011; 8: 189-200.
10.1038/nrgastro.2011.20
CAS PubMed Web of Science® Google Scholar
3Rege TA, Hagood JS. Thy-1 as a regulator of cell-cell and cell-matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. FASEB J. 2006; 20: 1045-1054.
10.1096/fj.05-5460rev
CAS PubMed Web of Science® Google Scholar
4Masson NM, Currie IS, Terrace JD, Garden OJ, Parks RW, Ross JA. Hepatic progenitor cells in human fetal liver express the oval cell marker Thy-1. Am J Physiol Gastrointest Liver Physiol. 2006; 291. G45-G54.
10.1152/ajpgi.00465.2005
PubMed Web of Science® Google Scholar
5Weiss TS, Lichtenauer M, Kirchner S, et al. Hepatic progenitor cells from adult human livers for cell transplantation. Gut. 2008; 57: 1129-1138.
10.1136/gut.2007.143321
CAS PubMed Web of Science® Google Scholar
6Donnenberg VS, Donnenberg AD, Zimmerlin L, et al. Localization of CD44 and CD90 positive cells to the invasive front of breast tumors. Cytometry B Clin Cytom. 2010; 78: 287-301.
10.1002/cyto.b.20530
CAS PubMed Web of Science® Google Scholar
7Tang K, Dai Y, Tong M, et al. A CD90⁺ tumor-initiating cell population with an aggressive signature and metastatic capacity in esophageal cancer. Cancer Res. 2013; 73: 2322-2332.
10.1158/0008-5472.CAN-12-2991
CAS PubMed Web of Science® Google Scholar
8Zhu J, Thakolwiboon S, Liu X, Zhang M, Lubman DM. Overexpression of CD90 (Thy-1) in pancreatic adenocarcinoma present in the tumor microenvironment. PLOS One. 2014; 9: e115507.
10.1371/journal.pone.0115507
PubMed Web of Science® Google Scholar
9Cheng BQ, Jiang Y, Li DL, Fan JJ, Ma M. Up-regulation of thy-1 promotes invasion and metastasis of hepatocarcinomas. Asian Pac J Cancer Prev. 2012; 13: 1349-1353.
10.7314/APJCP.2012.13.4.1349
PubMed Google Scholar
10Sukowati CHC, Anfuso B, Torre G, Francalanci P, Crocè LS, Tiribelli C. The expression of CD90/Thy-1 in hepatocellular carcinoma: an in vivo and in vitro study. PLOS One. 2013; 8: e76830.
10.1371/journal.pone.0076830
CAS PubMed Web of Science® Google Scholar
11Ishii T, Yasuchika K, Suemori H, Nakatsuji N, Ikai I, Uemoto S. Alpha-fetoprotein producing cells act as cancer progenitor cells in human cholangiocarcinoma. Cancer Lett. 2010; 294: 25-34.
10.1016/j.canlet.2010.01.019
CAS PubMed Web of Science® Google Scholar
12Sasaki N, Ishii T, Kamimura R, et al. Alpha-fetoprotein-producing pancreatic cancer cells possess cancer stem cell characteristics. Cancer Lett. 2011; 308: 152-161.
10.1016/j.canlet.2011.04.023
CAS PubMed Web of Science® Google Scholar
13Ishii T, Fukumitsu K, Yasuchika K, et al. Effects of extracellular matrixes and growth factors on the hepatic differentiation of human embryonic stem cells. Am J Physiol Gastrointest Liver Physiol. 2008; 295: G313-G321.
10.1152/ajpgi.00072.2008
CAS PubMed Web of Science® Google Scholar
14Ishii T, Yasuchika K, Fujii H, et al. In vitro differentiation and maturation of mouse embryonic stem cells into hepatocytes. Exp Cell Res. 2005; 309: 68-77.
10.1016/j.yexcr.2005.05.028
CAS PubMed Web of Science® Google Scholar
15Ishii T, Yasuchika K, Machimoto T, et al. Transplantation of embryonic stem cell-derived endodermal cells into mice with induced lethal liver damage. Stem Cells. 2007; 25: 3252-3260.
10.1634/stemcells.2007-0199
CAS PubMed Web of Science® Google Scholar
16Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009; 9: 265-273.
10.1038/nrc2620
CAS PubMed Web of Science® Google Scholar
17Wang Z, Ma Q, Liu Q, et al. Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway. Br J Cancer. 2008; 99: 1695-1703.
10.1038/sj.bjc.6604745
CAS PubMed Web of Science® Google Scholar
18Crawford HC, Fingleton BM, Rudolph-Owen LA, et al. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene. 1999; 18: 2883-2891.
10.1038/sj.onc.1202627
CAS PubMed Web of Science® Google Scholar
19Chuaysri C, Thuwajit P, Paupairoj A, Chau-In S, Suthiphongchai T, Thuwajit C. Alpha-smooth muscle actin-positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma. Oncol Rep. 2009; 21: 957-969.
CAS PubMed Web of Science® Google Scholar
20Schliekelman MJ, Creighton CJ, Baird BN, et al. Thy-1+ Cancer-associated fibroblasts adversely impact lung cancer prognosis. Sci Rep. 2017; 7: 6478.
10.1038/s41598-017-06922-5
PubMed Web of Science® Google Scholar
21Hu T, Yao Y, Yu S, et al. SDF-1/CXCR4 promotes epithelial–mesenchymal transition and progression of colorectal cancer by activation of the Wnt/β-catenin signaling pathway. Cancer Lett. 2014; 354: 417-426.
10.1016/j.canlet.2014.08.012
CAS PubMed Web of Science® Google Scholar
22Zhao S, Wang J, Qin C. Blockade of CXCL12/CXCR4 signaling inhibits intrahepatic cholangiocarcinoma progression and metastasis via inactivation of canonical Wnt pathway. J Exp Clin Cancer Res. 2014; 33: 1-12.
10.1186/s13046-014-0103-8
CAS PubMed Web of Science® Google Scholar
23Yang P, Wang G, Huo H, Li Q, Zhao Y, Liu Y. SDF-1/CXCR4 signaling up-regulates survivin to regulate human sacral chondrosarcoma cell cycle and epithelial-mesenchymal transition via ERK and PI3K/AKT pathway. Med Oncol. 2015; 32: 377.
10.1007/s12032-014-0377-x
CAS PubMed Web of Science® Google Scholar
24Noë V, Fingleton B, Jacobs K, et al. Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. J Cell Sci. 2001; 114: 111-118.
CAS PubMed Web of Science® Google Scholar
25Miwa S, Miyagawa S, Soeda J, Kawasaki S. Matrix metalloproteinase-7 expression and biologic aggressiveness of cholangiocellular carcinoma. Cancer. 2002; 94: 428-434.
10.1002/cncr.10235
CAS PubMed Web of Science® Google Scholar
26Hirashita T, Iwashita Y, Ohta M, et al. Expression of matrix metalloproteinase-7 is an unfavorable prognostic factor in intrahepatic cholangiocarcinoma. J Gastrointest Surg. 2012; 16: 842-848.
10.1007/s11605-011-1813-2
PubMed Web of Science® Google Scholar
27MacDonald BT, Tamai K, He X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17: 9-26.
10.1016/j.devcel.2009.06.016
CAS PubMed Web of Science® Google Scholar
28Emami KH, Nguyen C, Ma H, et al. A small molecule inhibitor of beta-catenin/CREB-binding protein transcription [corrected]. Proc Natl Acad Sci USA. 2004; 101: 12682-12687.
10.1073/pnas.0404875101
CAS PubMed Web of Science® Google Scholar
29Arensman MD, Telesca D, Lay AR, et al. The CREB-binding protein inhibitor ICG-001 suppresses pancreatic cancer growth. Mol Cancer Ther. 2014; 13: 2303-2314.
10.1158/1535-7163.MCT-13-1005
CAS PubMed Web of Science® Google Scholar
30Zhao B, Zhao H, Zhao N, Zhu X. Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment. J Hepatobiliary Pancreat Surg. 2002; 9: 497-502.
10.1007/s005340200062
CAS PubMed Google Scholar

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Volume118, Issue4

September 15, 2018

Pages 664-674

CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

Abstract

Background and Objectives

Methods

Results

Conclusion

CONFLICTS OF INTEREST

Supporting Information

REFERENCES

Citing Literature

References

Information

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CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis

Abstract

Background and Objectives

Methods

Results

Conclusion

CONFLICTS OF INTEREST

Supporting Information

REFERENCES

Citing Literature

References

Related

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