This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Su, L. Articles by Xiong, S. Search for Related Content PubMed PubMed Citation Articles by Su, L. Articles by Xiong, S.

Differential Expression of CXCR4 Is Associated with the Metastatic Potential of Human Non–Small Cell Lung Cancer Cells

Authors' Affiliations: ¹ Department of Immunology and Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University and ² Immunology Division of E-Institutes of Shanghai Universities, Shanghai, People's Republic of China

Requests for reprints: Sidong Xiong, Department of Immunology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China. Phone: 86-21-5423-7749; Fax: 86-21-5423-7749; E-mail: sdxiongfd{at}126.com.

Purpose: To evaluate the relation between CXCR4 expression and the presence of metastatic disease in human non–small cell lung cancer (NSCLC) patients and investigate whether modulation of CXCR4 expression could serve as a potential pathway in preventing metastasis of NSCLC.

Experimental Design: CXCR4 expression in 36 patients with NSCLC and 10 normal lung tissues was detected by real-time PCR and immunohistochemistry. CXCR4 expression in two human NSCLC clones (95C and 95D) with different metastatic potential was determined by real-time PCR and flow cytometry. 95C and 95D cells were transfected with the plasmid DNA containing CXCR4 coding gene or CXCR4 antisense nucleotide fragment, respectively, and the effects on in vitro cell migration, invasion, and adhesion and in vivo metastasis were measured.

Results: Up-regulated expression of CXCR4 was detected in 34 tumors, which were further divided into 17 high expression cancers and 17 low expression cancers by their staining intensities. High CXCR4 tumors (13 of 17) were more prone to clinical metastasis in comparison with low expression tumors. CXCR4 was differentially expressed in 95C and 95D cells with low or high metastatic potential, and the surface expression of CXCR4 were 50% up-regulated or down-regulated following the stable transfection. The metastatic potential of NSCLC in vitro, such as migration, invasion, and adhesion, were significantly enhanced or impaired. In addition, neutralizing the interactions of stromal cell–derived factor-1/CXCR4 in vitro with CXCR4-specific antibodies inhibited the CXCR4-dependent migration, invasion, and adhesion. Furthermore, s.c. inoculation of lung cancer cells with low expression of CXCR4 in nude mice showed 0- to 2-fold decrease in lung metastatic foci than that with high expression of CXCR4.

Conclusions: Differential expression of CXCR4 is associated with the metastatic potential of human NSCLC, raising the possibility that blockade of CXCR4/stromal cell–derived factor-1 interaction may lead the way to design novel therapeutic tools for the treatment of metastatic NSCLC patients.

This article has been cited by other articles:

				P. L. Wagner, E. Hyjek, M. F. Vazquez, D. Meherally, Y. F. Liu, P. A. Chadwick, T. Rengifo, G. L. Sica, J. L. Port, P. C. Lee, et al. CXCL12 and CXCR4 in adenocarcinoma of the lung: association with metastasis and survival. J. Thorac. Cardiovasc. Surg., March 1, 2009; 137(3): 615 - 621. [Abstract] [Full Text] [PDF]

				M. A. Mines, J. S. Goodwin, L. E. Limbird, F.-F. Cui, and G.-H. Fan Deubiquitination of CXCR4 by USP14 Is Critical for Both CXCL12-induced CXCR4 Degradation and Chemotaxis but Not ERK Activation J. Biol. Chem., February 27, 2009; 284(9): 5742 - 5752. [Abstract] [Full Text] [PDF]

				P. L. Wagner, T.-A. Moo, N. Arora, Y.-F. Liu, R. Zarnegar, T. Scognamiglio, and T. J. Fahey III The Chemokine Receptors CXCR4 and CCR7 are Associated with Tumor Size and Pathologic Indicators of Tumor Aggressiveness in Papillary Thyroid Carcinoma Ann. Surg. Oncol., October 1, 2008; 15(10): 2833 - 2841. [Abstract] [Full Text] [PDF]

				Z. Miao, K. E. Luker, B. C. Summers, R. Berahovich, M. S. Bhojani, A. Rehemtulla, C. G. Kleer, J. J. Essner, A. Nasevicius, G. D. Luker, et al. CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature PNAS, October 2, 2007; 104(40): 15735 - 15740. [Abstract] [Full Text] [PDF]