Open Access Highly Accessed Research article

CXCR4 expression on circulating pan-cytokeratin positive cells is associated with survival in patients with advanced non-small cell lung cancer

Karen L Reckamp12*, Robert A Figlin1, Marie D Burdick3, Steven M Dubinett45, Robert M Elashoff6 and Robert M Strieter3

Author Affiliations

1 Department of Medical Oncology & Therapeutics Research, City of Hope and Beckman Research Institute, Duarte, USA

2 Department of Hematology & Hematopoeitic Transplantation Medicine, City of Hope and Beckman Research Institute, Duarte, USA

3 Department of Medicine, University of Virginia School of Medicine, Charlottesville, USA

4 Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, Los Angeles, USA

5 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, USA

6 Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, USA

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BMC Cancer 2009, 9:213  doi:10.1186/1471-2407-9-213

Published: 29 June 2009

Abstract

Background

The CXC chemokine, CXCL12, and its receptor, CXCR4 promote metastases of a variety of solid tumors, including non-small cell lung cancer (NSCLC). The expression of CXCR4 on tumor cells may represent a critical biomarker for their propensity to metastasize. This study was performed to evaluate the hypothesis that co-expression of pan-cytokeratin and CXCR4 may be a prognostic marker for patients with advanced NSCLC.

Methods

We evaluated CXCR4 levels on circulating pan-cytokeratin positive cells from patients with NSCLC. NSCLC tumor and metastases were also assessed for the presence of CXCR4.

Results

Pan-cytokeratin positive cells were increased in the circulation of patients with NSCLC, as compared to normal control subjects. Patients with pan-cytokeratin +/CXCR4+ = 2,500 cells/ml had a significant improvement in median survival when compared with patients with pan-cytokeratin +/CXCR4+ >2,500 cells/ml (not achieved versus 14 weeks). CXCR4 expression was found on NSCLC tumors and at sites of tumor metastasis.

Conclusion

This study suggests that CXCR4 may be a prognostic marker in NSCLC, and provides hypothesis-generating results, which may be important in determining metastatic potential. In future studies, we will prospectively evaluate the prognostic significance of pan-cytokeratin/CXCR4+ cells, and determine the mechanisms involved in the regulation of CXCR4 expression on tumor cells in a larger patient population.