Advertisement

Annals of Surgical Oncology

, Volume 19, Supplement 3, pp 365–374 | Cite as

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

  • Jian-Qiang Guo
  • Wei-Hua Yu
  • Hong-Juan Wang
  • Bin Liu
  • Kong-Xi Zhu
  • Qing-Hui Zhang
  • Ting-Guo Zhang
  • Wei-Hua Xu
  • Hong-Bo Wang
  • Hong-Li Wu
  • Cheng-Jun Zhou
Translational Research and Biomarkers

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.

Keywords

CD105 Intestinal Metaplasia Normal Mucosa Neoplastic Lesion Prostate Intraepithelial Neoplasia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 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.PubMedGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Wagener C, Ergun S. Angiogenic properties of the carcinoembryonic antigen-related cell adhesion molecule 1. Exp Cell Res. 2000;261:19–24.PubMedCrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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,PubMedCrossRefGoogle Scholar
  13. 13.
    Gray-Owen SD, Blumberg RS. CEACAM1: contact-dependent control of immunity. Immunology. 2006;6:433–46.PubMedGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 16.
    Moh MC, Shen S. The roles of cell adhesion molecules in tumor suppression and cell migration. Cell Adh Migr. 2009;3:334–6.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 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.CrossRefGoogle Scholar
  21. 21.
    Seon BK. Expression of endoglin (CD105) in tumor blood vessels. Int J Cancer 2002;99:310–1.PubMedCrossRefGoogle Scholar
  22. 22.
    Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: evidence and potential applications. FASEB J. 2003;17:984–92.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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. 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.PubMedGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Jian-Qiang Guo
    • 1
  • Wei-Hua Yu
    • 1
  • Hong-Juan Wang
    • 1
  • Bin Liu
    • 1
  • Kong-Xi Zhu
    • 1
  • Qing-Hui Zhang
    • 2
  • Ting-Guo Zhang
    • 2
  • Wei-Hua Xu
    • 1
  • Hong-Bo Wang
    • 1
  • Hong-Li Wu
    • 1
  • Cheng-Jun Zhou
    • 1
  1. 1.Department of Digestive Disease, The Second HospitalShandong UniversityJinanPeople’s Republic of China
  2. 2.Department of PathologyShandong University School of MedicineJinanPeople’s Republic of China

Personalised recommendations