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


CONCLUSIONS
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.
Reckamp
Karen L
KL
Department of Medical Oncology & Therapeutics Research, City of Hope and Beckman Research Institute, Duarte, CA, USA. kreckamp@coh.org
Figlin
Robert A
RA
Burdick
Marie D
MD
Dubinett
Steven M
SM
Elashoff
Robert M
RM
Strieter
Robert M
RM
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000096:biosynthesis*
C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D007633:Keratins