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Different Expression Patterns of CEACAM1 and its Impacts on Angiogenesis in Gastric Nonneoplastic and Neoplastic Lesions

  • Translational Research and Biomarkers
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Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Objective

This study was designed to investigate the expression patterns of CEACAM1 and its relationship with angiogenesis in nonneoplastic and neoplastic gastric lesions.

Methods

CEACAM1 and TGF-β expression was detected by immunohistochemical staining and dual-labeling immunohistochemical staining in neoplastic and nonneoplastic lesions. MVD-CD31 and MVD-CD105 were counted in CEACAM1-positive areas by dual-labeling immunohistochemistry.

Results

There was no expression of CEACAM1 in normal gastric mucosa. In IM and GIN, CEACAM1 was mainly expressed with membranous pattern. CEACAM1 was expressed with membranous pattern in well-differentiated adenocarcinoma, with cytoplasmic pattern in poorly differentiated adenocarcinoma, and with cytoplasmic and membranous pattern mixed together in intermediately adenocarcinoma. The expression patterns of CEACAM1 showed a significant difference (P < 0.05) in nonneoplastic and neoplastic lesions. Coexpression of CEACAM1 and TGF-β was elevated and significantly different from nonneoplastic to neoplastic lesions (P < 0.05). Moreover, CEACAM1 and TGF-β coexpression were related to carcinoma progression (r = 0.35; P < 0.05). MVD-CD31 and MVD-CD105 showed significant differences from nonneoplastic to neoplastic lesions (P < 0.05).

Conclusions

CEACAM1 has different expression patterns in nonneoplastic and neoplastic lesions. The coexpression of CEACAM1 and TGF-β increased from nonneoplastic to neoplastic lesions and may be related with tumor progression via promoting tumorous angiogenesis.

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References

  1. Singer BB, Scheffrahn I, Obrink B. The tumor growth inhibiting cell adhesion molecule CEACAM1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation. Cancer Res. 2000;60:1236–44.

    PubMed  CAS  Google Scholar 

  2. Nakajima A, Iijima H, Neurath MF, Nagaishi T, Nieuwenhuis EE, Raychowdhury R, Glickman J, et al. Activation-induced expression of carcinoembryonic antigen-cell adhesion molecule 1 regulates mouse T lymphocyte function. J Immunol. 2002;168:1028-35.

    PubMed  CAS  Google Scholar 

  3. Chen D, Iijima H, Nagaishi T, Nakajima A, Russell S, Raychowdhury R, Morales V, et al. Carcinoembryonic antigen-related cellular adhesion molecule 1 isoforms alternatively inhibit and costimulate human T cell function. J Immunol. 2004;172:3535–43.

    PubMed  CAS  Google Scholar 

  4. Ergun S, Kilic N, Ziegeler G, Hansen A, Nollau P, Gotze J, et al. CEA-related cell adhesion molecule 1: a potent angiogenic factor and a major effector of vascular endothelial growth factor. Mol Cell. 2000;5:311–20.

    Article  PubMed  CAS  Google Scholar 

  5. Wagener C, Ergun S. Angiogenic properties of the carcinoembryonic antigen-related cell adhesion molecule 1. Exp Cell Res. 2000;261:19–24.

    Article  PubMed  CAS  Google Scholar 

  6. Kilic N, Oliveira-Ferrer L, Wurmbach JH, Loges S, et al. Pro-angiogenic signaling by the endothelial presence of CEACAM1. J Bio Chem. 2005;280(3):2361–9.

    Article  CAS  Google Scholar 

  7. Oliveira-Ferrer L, Tilki D, Ziegeler G, Hauschild J, Loges S, et al. Dual role of carcinoembryonic antigen-related cell adhesion molecule 1 in angiogenesis and invasion of human urinary bladder cancer. Cancer Res. 2004;64:8932–8.

    Article  PubMed  CAS  Google Scholar 

  8. Kammerer R, Riesenberg R, Weiler C, Lohrmann J, Achleypen J, Zimmermann W. The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma. J Pathol. 2004;204:258–67.

    Article  PubMed  CAS  Google Scholar 

  9. Laack E, Nikbakht H, Petera A, Kugler C, Jasiewicz Y, et al. Expression of CEACAM1 in adenocarcinoma of the lung: a factor of independent prognostic significance. J Clin Oncol. 2002;20:4279–84.

    Article  PubMed  Google Scholar 

  10. Kang W-Y, Chen W-T, Wu M-T. The expression of CD66a and possible roles in colorectal adenoma and adenocarcinoma. Int J Colorectal Dis. 2007;22:869–74.

    Article  PubMed  Google Scholar 

  11. Muller MM, Singer BB, Klaile E, et al. Transmembrane CEACAM1 affects integrin-dependent signaling and regulates extracellular matrix protein-specific morphology and migration of endothelial cells. Blood. 2005; 105: 3925–3934.

    Article  PubMed  Google Scholar 

  12. Tilki D, Irmak S, Oliveira-Ferrer L, et al. CEA-related cell adhesion molecule-1 is involved in angiogenic switch in prostate cancer. Oncogene. 2006;25:4965–74,

    Article  PubMed  CAS  Google Scholar 

  13. Gray-Owen SD, Blumberg RS. CEACAM1: contact-dependent control of immunity. Immunology. 2006;6:433–46.

    PubMed  CAS  Google Scholar 

  14. Riethdorf L, Lisboa BW, Henkel U, Naumann M, Wagener C, Löning T. Differential expression of CD66a (BGP), a Cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland. J Histochem Cytochem. 1997;45:957–64.

    Article  PubMed  CAS  Google Scholar 

  15. Volpert O, Luo W, Liu TJ, Vicky T, et al. Inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1. J Bio Chem. 2002; 277(38): 35696–35702.

    Article  CAS  Google Scholar 

  16. Moh MC, Shen S. The roles of cell adhesion molecules in tumor suppression and cell migration. Cell Adh Migr. 2009;3:334–6.

    Article  PubMed  Google Scholar 

  17. Song JH, Cao Z, Yoon JH, et al. Genetic alterations and expression pattern of CEACAM1 in colorectal adenomas and cancers. Pathol Oncol Res. 2011; 17:67–74.

    Article  PubMed  CAS  Google Scholar 

  18. Nouvion AL, Oubaha M, Leblanc S, et al. CEACAM1: a key regulator of vascular permeability. J Cell Sci. 2010;123(Pt 24):4221–30.

    Article  PubMed  CAS  Google Scholar 

  19. Fonsatti E, Sigalotti L, Arslan P, Altomonte M, Maio M. Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical potential in human malignancies. Curr Cancer Drug Targets. 2003;3(6):427–32.

    Article  CAS  Google Scholar 

  20. Li CG, Wilson PB, Bernabeu C, Raab U, Wang JM, Kumar S. Immunodetection and characterisation of soluble CD105-TGFbeta complexes. J Immunol Method. 1998;218:85–93.

    Article  CAS  Google Scholar 

  21. Seon BK. Expression of endoglin (CD105) in tumor blood vessels. Int J Cancer 2002;99:310–1.

    Article  PubMed  CAS  Google Scholar 

  22. Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications. FASEB J. 2003;17:984–92.

    Article  PubMed  CAS  Google Scholar 

  23. Li C, Gardy R, Seon BK, et al. Both high intratumoral microvessel density determined using CD105 antibody and elevated plasma levels of CD105 in colorectal cancer patients correlate with poor prognosis. Br J Cancer. 2003;88:1424–31.

    Article  PubMed  CAS  Google Scholar 

  24. Yagasaki H, Kawata N, Takimoto Y, Nemoto N. Histopathological analysis of angiogenic factors in renal cell carcinoma. Int J Urol. 2003;10:220–7.

    Article  PubMed  Google Scholar 

  25. Kumar S, Ghellal A, Li C, Byrne G, Haboubi N, Wang JM, Bundred N. Breast carcinoma: vascular density determined using CD105 antibody correlates with tumor prognosis. Cancer Res. 1999;59:856–61.

    PubMed  CAS  Google Scholar 

  26. Tanaka F, Otake Y, Yanagihara K, et al. Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody. Clin Cancer Res. 2001;7:3410–5.

    PubMed  CAS  Google Scholar 

  27. Hamilton SR, Aaltonen LA. WHO classification of tumours: Pathology and genetics of tumours of the digestive system. IARC Press: Lyon; 2000.

    Google Scholar 

  28. Kleinerman DI, Troncoso P, Lin SH, Pisters LL, Sherwood ER, Brooks T, et al. Consistent expression of an epithelial cell adhesion molecule (c-cam) during human prostate development and loss of expression in prostate cancer: implication as a tumor suppressor. Cancer Res. 1995;55:1215–20.

    PubMed  CAS  Google Scholar 

  29. Shinozuka K, Uzawa K, Fushimi K, Yamano Y, Shiiba M, Bukawa H, et al. Downregulation of carcinoembryonic antigen-related cell adhesion molecule 1 in oral squamous cell carcinoma: correlation with tumor progression and poor prognosis. Oncology. 2009;76:387-97.

    Article  PubMed  CAS  Google Scholar 

  30. Riethdorf L, Lisboa BW, Henkel U, Naumann M, Wagener C, Löning T. Differential expression of CEACAM1 (bgp), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant and malignant lesions of the human mammary gland. J Histochem Cytochem. 1997;45:957–63.

    Article  PubMed  CAS  Google Scholar 

  31. Yamato Y, Koike T, Yoshiya K, Fukui M, Kitahara A, Toyabe S. Factors influencing long-term survival and surgical indications for pulmonary metastasectomy for metastases from colorectal cancer. Thoracic Cancer. 2011. doi:10.1111/j.1759-7714.2011.00044.x.

  32. Ebrahimnejad A, Streichert T, Nollau P, Horst AK, Wagener C, Bamberger AM, et al. CEACAM1 enhances invasion and migration of melanocytic and melanoma cells. Am J Pathol. 2004;165:1781–7.

    Article  PubMed  CAS  Google Scholar 

  33. Liu W, Wei W, Winer D, Bamberger AM, Bamberger C, Wagener C, et al. Ceacam1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases. Oncogene. 2007;26:2747–58.

    Article  PubMed  Google Scholar 

  34. Zhou CJ, Liu B, Zhu KX, et al. The different expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and possible roles in gastric carcinomas. Pathol Res Pract. 2009;205(7):483–9.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Digestive Disease, The Second Hospital, Shandong University, Jinan, Shandong, People’s Republic of China

    Jian-Qiang Guo MD, Wei-Hua Yu MD, Hong-Juan Wang MD, Bin Liu MD, Kong-Xi Zhu MD, Wei-Hua Xu MD, Hong-Bo Wang MD, Hong-Li Wu MD & Cheng-Jun Zhou MD

  2. Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, People’s Republic of China

    Qing-Hui Zhang MD & Ting-Guo Zhang MD

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  1. Jian-Qiang Guo MD
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Correspondence to Cheng-Jun Zhou MD.

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Guo, JQ., Yu, WH., Wang, HJ. et al. Different Expression Patterns of CEACAM1 and its Impacts on Angiogenesis in Gastric Nonneoplastic and Neoplastic Lesions. Ann Surg Oncol 19 (Suppl 3), 365–374 (2012). https://doi.org/10.1245/s10434-011-1811-3

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  • DOI: https://doi.org/10.1245/s10434-011-1811-3

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