Tumor Biology

, Volume 32, Issue 1, pp 197–202 | Cite as

Expression of the chemokine receptor CCR6 correlates with a favorable prognosis in patients with adenocarcinoma of the lung

  • Yoshihiro Minamiya
  • Hajime Saito
  • Naoko Takahashi
  • Manabu Ito
  • Hiroshi Toda
  • Takashi Ono
  • Hayato Konno
  • Satoru Motoyama
  • Jun-ichi Ogawa
Research Article

Abstract

The relation between CCR6 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood and remains controversial. We, therefore, investigated the relationship between CCR6 expression and prognosis in patients with adenocarcinoma of the lung. We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of CCR6 mRNA in tumor samples from 84 patients with adenocarcinoma of the lung. We then correlated the levels of CCR6 mRNA with known clinicopathological features. The 5-year disease-free survival rate among patients expressing higher levels of CCR6 mRNA was significantly better than among those expressing lower levels (P = 0.009 by log-rank test). Multivariate Cox proportional hazard analyses revealed, being male [hazard ratio, 3.94; 95% confidence interval (CI), 1.58 to 10.36; P = 0.003], tumor size >30 mm (hazard ratio, 2.46; 95% CI, 1.08 to 5.73; P = 0.030), nodal metastasis (hazard ratio, 7.66; 95% CI, 2.62 to 23.3; P = 0.0002), and CCR6 (hazard ratio, 0.34; 95% CI, 0.11 to 0.93; P = 0.034) to be independent factors affecting the 5-year disease-free survival rate. Greater expression of CCR6 by tumor cells is an independent predictor of a better prognosis in patients with adenocarcinoma of the lung.

Keywords

Chemokine receptor Lung cancer Prognosis Adenocarcinoma 

Notes

Conflict of interest statement

None declared.

References

  1. 1.
    Mareel M, Leroy A. Clinical, cellular, and molecular aspects of cancer invasion. Physiol Rev. 2003;83:337–76.PubMedGoogle Scholar
  2. 2.
    Wang JM, Deng X, Gong W, Su S. Chemokines and their role in tumor growth and metastasis. J Immunol Methods. 1998;220:1–17.CrossRefPubMedGoogle Scholar
  3. 3.
    Schutyser E, Struyf S, Van Damme J. The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev. 2003;14:409–26.CrossRefPubMedGoogle Scholar
  4. 4.
    Ghadjar P, Rubie C, Aebersold DM, Keilholz U. The chemokine CCL20 and its receptor CCR6 in human malignancy with focus on colorectal cancer. Int J Cancer. 2009;125:741–5.CrossRefPubMedGoogle Scholar
  5. 5.
    Dellacasagrande J, Schreurs OJ, Hofgaard PO, Omholt H, Steinsvoll S, Schenck K, et al. Liver metastasis of cancer facilitated by chemokine receptor CCR6. Scand J Immunol. 2003;57:534–44.CrossRefPubMedGoogle Scholar
  6. 6.
    Ghadjar P, Loddenkemper C, Coupland SE, Stroux A, Noutsias M, Thiel E, et al. Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer. J Cancer Res Clin Oncol. 2008;134:1181–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Brand S, Olszak T, Beigel F, Diebold J, Otte JM, Eichhorst ST, et al. Cell differentiation dependent expressed CCR6 mediates ERK-1/2, SAPK/JNK, and Akt signaling resulting in proliferation and migration of colorectal cancer cells. J Cell Biochem. 2006;97:709–23.CrossRefPubMedGoogle Scholar
  8. 8.
    Rubie C, Frick VO, Wagner M, Weber C, Kruse B, Kempf K, et al. Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases. World J Gastroenterol. 2006;12:6627–33.PubMedGoogle Scholar
  9. 9.
    Rubie C, Oliveira V, Kempf K, Wagner M, Tilton B, Rau B, et al. Involvement of chemokine receptor CCR6 in colorectal cancer metastasis. Tumour Biol. 2006;27:166–74.CrossRefPubMedGoogle Scholar
  10. 10.
    Uchida H, Iwashita Y, Sasaki A, Shibata K, Matsumoto T, Ohta M, et al. Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma. J Gastroenterol Hepatol. 2006;21:161–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Wang J, Xi L, Gooding W, Godfrey TE, Ferris RL. Chemokine receptors 6 and 7 identify a metastatic expression pattern in squamous cell carcinoma of the head and neck. Adv Otorhinolaryngol. 2005;62:121–33.PubMedGoogle Scholar
  12. 12.
    Wang J, Xi L, Hunt JL, Gooding W, Whiteside TL, Chen Z, et al. Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype. Cancer Res. 2004;64:1861–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Sutherland A, Mirjolet JF, Maho A, Parmentier M. Expression of the chemokine receptor CCR6 in the Lewis lung carcinoma (LLC) cell line reduces its metastatic potential in vivo. Cancer Gene Ther. 2007;14:847–57.CrossRefPubMedGoogle Scholar
  14. 14.
    Naruke T, Suemasu K, Ishikawa S. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg. 1978;76:832–9.PubMedGoogle Scholar
  15. 15.
    Kimsey TF, Campbell AS, Albo D, Wilson M, Wang TN. Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J. 2004;10:374–80.CrossRefPubMedGoogle Scholar
  16. 16.
    Reibman J, Hsu Y, Chen LC, Bleck B. Gordon T. Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter. Am J Respir Cell Mol Biol. 2003;28:648–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Fitzhugh DJ, Naik S, Caughman SW, Hwang ST. C-C chemokine receptor 6 is essential for arrest of a subset of memory T cells on activated dermal microvascular endothelial cells under physiologic flow conditions in vitro. J Immunol. 2000;165:6677–81.PubMedGoogle Scholar
  18. 18.
    Ho C, Murray N, Laskin J, Melosky B, Anderson H, Bebb G. Asian ethnicity and adenocarcinoma histology continues to predict response to gefitinib in patients treated for advanced non-small cell carcinoma of the lung in North America. Lung Cancer. 2005;49:225–31.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2010

Authors and Affiliations

  • Yoshihiro Minamiya
    • 1
    • 2
  • Hajime Saito
    • 1
  • Naoko Takahashi
    • 1
  • Manabu Ito
    • 1
  • Hiroshi Toda
    • 1
  • Takashi Ono
    • 1
  • Hayato Konno
    • 1
  • Satoru Motoyama
    • 1
  • Jun-ichi Ogawa
    • 1
  1. 1.Department of Chest, Breast and Endoclinologic SurgeryAkita University Graduate School of MedicineAkita CityJapan
  2. 2.Division of Thoracic SurgeryAkita University School of MedicineAkita CityJapan

Personalised recommendations